MANINDRA Bera

@yale.edu

Postdoctoral Associate, Department of Cell Biology
Yale School of Medicine

MANINDRA Bera


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https://researchid.co/manindra.bera

RESEARCH INTERESTS

Biophysics, Biochemistry, Neuroscience, Membrane Biology, Nuclear Biology, Mechanotransduction, Biomechanics
17

Scopus Publications

424

Scholar Citations

11

Scholar h-index

11

Scholar i10-index

Scopus Publications

  • Highly stable planar asymmetric suspended membranes for investigating protein dynamics and membrane fusion
    Manindra Bera, Ramalingam Venkat Kalyana Sundaram, Jeff Coleman, Atrouli Chatterjee, Sikha Thoduvayil, Frederic Pincet, Sathish Ramakrishnan
    Nature Protocols, 2025
  • Two successive oligomeric Munc13 assemblies scaffold vesicle docking and SNARE assembly to support neurotransmitter release
    Manindra Bera, Kirill Grushin, R. Venkat Kalyana Sundaram, Jasmine S. Hinzen, Joyce Chen, Atrouli Chatterjee, Abhijith Radhakrishnan, Seong Lee, Murugesh Padmanarayana, Jeff Coleman, Frédéric Pincet, James E. Rothman, Jeremy S. Dittman
    Nature Communications, 2025
    The critical protein Munc13 serves numerous roles in the docking and priming of synaptic vesicles. On the presynaptic plasma membrane, Munc13 is organized into nanoclusters corresponding to release sites where synaptic vesicles dock and fuse. However, it is currently not known whether there is any organization of Munc13 monomers within the nanoclusters. Recent work suggests that Munc13 may spontaneously self-organize into homo-oligomers, raising the possibility that synaptic nanoclusters comprise organized assemblies of Munc13. Here we investigate the functional impact of two distinct Munc13 core domain oligomers comprising C1-C2B-MUN-C2C both in vitro and in vivo. Interface mutations that specifically destabilized oligomeric assemblies of Munc13 disrupted vesicle docking, trans-SNARE formation, and Ca2+-triggered vesicle fusion in vitro and impaired neurotransmitter secretion and motor nervous system function in vivo. We suggest that a sequence of oligomeric Munc13 complexes rapidly couple vesicle docking to vesicle priming via the assembly of a precise number of SNAREs. The presynaptic protein Munc13 forms nanoclusters at synaptic release sites, but its internal organization is unclear. Here, the authors show that two distinct ordered Munc13 oligomers couple synaptic vesicle docking and SNARE assembly to regulate neurotransmission
  • Minimal presynaptic protein machinery governing diverse kinetics of calcium-evoked neurotransmitter release
    Dipayan Bose, Manindra Bera, Christopher A. Norman, Yulia Timofeeva, Kirill E. Volynski, Shyam S. Krishnakumar
    Nature Communications, 2024
    Neurotransmitters are released from synaptic vesicles with remarkable precision in response to presynaptic calcium influx but exhibit significant heterogeneity in exocytosis timing and efficacy based on the recent history of activity. This heterogeneity is critical for information transfer in the brain, yet its molecular basis remains poorly understood. Here, we employ a biochemically-defined fusion assay under physiologically relevant conditions to delineate the minimal protein machinery sufficient to account for various modes of calcium-triggered vesicle fusion dynamics. We find that Synaptotagmin-1, Synaptotagmin-7, and Complexin synergistically restrain SNARE complex assembly, thus preserving vesicles in a stably docked state at rest. Upon calcium activation, Synaptotagmin-1 induces rapid vesicle fusion, while Synaptotagmin-7 mediates delayed fusion. Competitive binding of Synaptotagmin-1 and Synaptotagmin-7 to the same SNAREs, coupled with differential rates of calcium-triggered fusion clamp reversal, govern the overall kinetics of vesicular fusion. Under conditions mimicking sustained neuronal activity, the Synaptotagmin-7 fusion clamp is destabilized by the elevated basal calcium concentration, thereby enhancing the synchronous component of fusion. These findings provide a direct demonstration that a small set of proteins is sufficient to account for how nerve terminals adapt and regulate the calcium-evoked neurotransmitter exocytosis process to support their specialized functions in the nervous system.
  • Turbocharging synaptic transmission
    James E. Rothman, Kirill Grushin, Manindra Bera, Frederic Pincet
    FEBS Letters, 2023
    Evidence from biochemistry, genetics, and electron microscopy strongly supports the idea that a ring of Synaptotagmin is central to the clamping and release of synaptic vesicles (SVs) for synchronous neurotransmission. Recent direct measurements in cell‐free systems suggest there are 12 SNAREpins in each ready‐release vesicle, consisting of six peripheral and six central SNAREpins. The six central SNAREpins are directly bound to the Synaptotagmin ring, are directly released by Ca++, and they initially open the fusion pore. The six peripheral SNAREpins are indirectly bound to the ring, each linked to a central SNAREpin by a bridging molecule of Complexin. We suggest that the primary role of peripheral SNAREpins is to provide additional force to ‘turbocharge’ neurotransmitter release, explaining how it can occur much faster than other forms of membrane fusion. The SV protein Synaptophysin forms hexamers that bear two copies of the v‐SNARE VAMP at each vertex, one likely assembling into a peripheral SNAREpin and the other into a central SNAREpin.
  • Rapid Quantification of First and Second Phase Insulin Secretion Dynamics using an In vitro Platform for Improving Insulin Therapy
    Sikha Thoduvayil, Jonathan S. Weerakkody, Ramalingam Venkat Kalyana Sundaram, Mackenzie Topper, Manindra Bera, Jeff Coleman, Xia Li, Malaiyalam Mariappan, Sathish Ramakrishnan
    Cell Calcium, 2023
  • Synaptophysin chaperones the assembly of 12 SNAREpins under each ready-release vesicle
    Manindra Bera, Abhijith Radhakrishnan, Jeff Coleman, R. Venkat K. Sundaram, Sathish Ramakrishnan, Frederic Pincet, James E. Rothman
    Proceedings of the National Academy of Sciences of the United States of America, 2023
    The synaptic vesicle protein Synaptophysin (Syp) has long been known to form a complex with the Vesicle associated soluble N-ethylmaleimide sensitive fusion protein attachment receptor (v-SNARE) Vesicle associated membrane protein (VAMP), but a more specific molecular function or mechanism of action in exocytosis has been lacking because gene knockouts have minimal effects. Utilizing fully defined reconstitution and single-molecule measurements, we now report that Syp functions as a chaperone that determines the number of SNAREpins assembling between a ready-release vesicle and its target membrane bilayer. Specifically, Syp directs the assembly of 12 ± 1 SNAREpins under each docked vesicle, even in the face of an excess of SNARE proteins. The SNAREpins assemble in successive waves of 6 ± 1 and 5 ± 2 SNAREpins, respectively, tightly linked to oligomerization of and binding to the vesicle Ca ++ sensor Synaptotagmin. Templating of 12 SNAREpins by Syp is likely the direct result of its hexamer structure and its binding of VAMP2 dimers, both of which we demonstrate in detergent extracts and lipid bilayers.
  • Roles for diacylglycerol in synaptic vesicle priming and release revealed by complete reconstitution of core protein machinery
    R. Venkat Kalyana Sundaram, Atrouli Chatterjee, Manindra Bera, Kirill Grushin, Aniruddha Panda, Feng Li, Jeff Coleman, Seong Lee, Sathish Ramakrishnan, Andreas M. Ernst, Kallol Gupta, James E. Rothman, Shyam S. Krishnakumar
    Proceedings of the National Academy of Sciences of the United States of America, 2023
    Here, we introduce the full functional reconstitution of genetically validated core protein machinery (SNAREs, Munc13, Munc18, Synaptotagmin, and Complexin) for synaptic vesicle priming and release in a geometry that enables detailed characterization of the fate of docked vesicles both before and after release is triggered with Ca 2+ . Using this setup, we identify new roles for diacylglycerol (DAG) in regulating vesicle priming and Ca 2+ -triggered release involving the SNARE assembly chaperone Munc13. We find that low concentrations of DAG profoundly accelerate the rate of Ca 2+ -dependent release, and high concentrations reduce clamping and permit extensive spontaneous release. As expected, DAG also increases the number of docked, release-ready vesicles. Dynamic single-molecule imaging of Complexin binding to release-ready vesicles directly establishes that DAG accelerates the rate of SNAREpin assembly mediated by chaperones, Munc13 and Munc18. The selective effects of physiologically validated mutations confirmed that the Munc18–Syntaxin–VAMP2 “template” complex is a functional intermediate in the production of primed, release-ready vesicles, which requires the coordinated action of Munc13 and Munc18.
  • Native Planar Asymmetric Suspended Membrane for Single-Molecule Investigations: Plasma Membrane on a Chip
    Ramalingam Venkat Kalyana Sundaram, Manindra Bera, Jeff Coleman, Jonathan S. Weerakkody, Shyam S. Krishnakumar, Sathish Ramakrishnan
    Small, 2022
    Cellular plasma membranes, in their role as gatekeepers to the external environment, host numerous protein assemblies and lipid domains that manage the movement of molecules into and out of cells, regulate electric potential, and direct cell signaling. The ability to investigate these roles on the bilayer at a single-molecule level in a controlled, in vitro environment while preserving lipid and protein architectures will provide deeper insights into how the plasma membrane works. A tunable silicon microarray platform that supports stable, planar, and asymmetric suspended lipid membranes (SLIM) using synthetic and native plasma membrane vesicles for single-molecule fluorescence investigations is developed. Essentially, a "plasma membrane-on-a-chip" system that preserves lipid asymmetry and protein orientation is created. By harnessing the combined potential of this platform with total internal reflection fluorescence (TIRF) microscopy, the authors are able to visualize protein complexes with single-molecule precision. This technology has widespread applications in biological processes that happen at the cellular membranes and will further the knowledge of lipid and protein assemblies.
  • Molecular determinants of complexin clamping and activation function
    Manindra Bera, Sathish Ramakrishnan, Jeff Coleman, Shyam S Krishnakumar, James E Rothman
    Elife, 2022
    Previously we reported that Synaptotagmin-1 and Complexin synergistically clamp the SNARE assembly process to generate and maintain a pool of docked vesicles that fuse rapidly and synchronously upon Ca2+ influx (Ramakrishnan et al., 2020). Here, using the same in vitro single-vesicle fusion assay, we determine the molecular details of the Complexin-mediated fusion clamp and its role in Ca2+-activation. We find that a delay in fusion kinetics, likely imparted by Synaptotagmin-1, is needed for Complexin to block fusion. Systematic truncation/mutational analyses reveal that continuous alpha-helical accessory-central domains of Complexin are essential for its inhibitory function and specific interaction of the accessory helix with the SNAREpins enhances this functionality. The C-terminal domain promotes clamping by locally elevating Complexin concentration through interactions with the membrane. Independent of their clamping functions, the accessory-central helical domains of Complexin also contribute to rapid Ca2+-synchronized vesicle release by increasing the probability of fusion from the clamped state.
  • Pulling the springs of a cell by single-molecule force spectroscopy
    Chandrayee Mukherjee, Manindra Bera, Sri Rama Koti Ainavarapu, Kaushik Sengupta
    Emerging Topics in Life Sciences, 2021
    The fundamental unit of the human body comprises of the cells which remain embedded in a fibrillar network of extracellular matrix proteins which in turn provides necessary anchorage the cells. Tissue repair, regeneration and reprogramming predominantly involve a traction force mediated signalling originating in the ECM and travelling deep into the cell including the nucleus via circuitry of spring-like filamentous proteins like microfilaments or actin, intermediate filaments and microtubules to elicit a response in the form of mechanical movement as well as biochemical changes. The ‘springiness’ of these proteins is highlighted in their extension–contraction behaviour which is manifested as an effect of differential traction force. Atomic force microscope (AFM) provides the magic eye to visualize and quantify such force-extension/indentation events in these filamentous proteins as well as in whole cells. In this review, we have presented a summary of the current understanding and advancement of such measurements by AFM based single-molecule force spectroscopy in the context of cytoskeletal and nucleoskeletal proteins which act in tandem to facilitate mechanotransduction.
  • Synergistic roles of synaptotagmin-1 and complexin in calcium-regulated neuronal exocytosis
    Sathish Ramakrishnan, Manindra Bera, Jeff Coleman, James E Rothman, Shyam S Krishnakumar
    Elife, 2020
  • Nuclear filaments: role in chromosomal positioning and gene expression
    Manindra Bera, Kaushik Sengupta
    Nucleus, 2020
  • RETREG1/FAM134B mediated autophagosomal degradation of AMFR/GP78 and OPA1 —a dual organellar turnover mechanism
    Debdatto Mookherjee, Subhrangshu Das, Rukmini Mukherjee, Manindra Bera, Swadhin Chandra Jana, Saikat Chakrabarti, Oishee Chakrabarti
    Autophagy, 2020
  • Chromosome territorial organization drives efficient protein complex formation: A hypothesis
    Yale Journal of Biology and Medicine, 2019
  • Synaptotagmin oligomers are necessary and can be sufficient to form a Ca 2+ -sensitive fusion clamp
    Sathish Ramakrishnan, Manindra Bera, Jeff Coleman, Shyam S. Krishnakumar, Frederic Pincet, James E. Rothman
    FEBS Letters, 2019
  • Significance of 1B and 2B domains in modulating elastic properties of lamin A
    Manindra Bera, Sri Rama Koti Ainavarapu, Kaushik Sengupta
    Scientific Reports, 2016
  • Characterization of unfolding mechanism of human lamin A Ig fold by single-molecule force spectroscopy-implications in EDMD
    Manindra Bera, Hema Chandra Kotamarthi, Subarna Dutta, Angana Ray, Saptaparni Ghosh, Dhananjay Bhattacharyya, Sri Rama Koti Ainavarapu, Kaushik Sengupta
    Biochemistry, 2014

RECENT SCHOLAR PUBLICATIONS

  • Highly stable planar asymmetric suspended membranes for investigating protein dynamics and membrane fusion
    M Bera, RV Kalyana Sundaram, J Coleman, A Chatterjee, S Thoduvayil, ...
    Nature Protocols 20 (12), 3582-3606 , 2025
    2025
    Citations: 3
  • Two successive oligomeric Munc13 assemblies scaffold vesicle docking and SNARE assembly to support neurotransmitter release
    M Bera, K Grushin, RV Kalyana Sundaram, JS Hinzen, J Chen, ...
    Nature Communications 16 (1), 7222 , 2025
    2025
    Citations: 9
  • Minimal presynaptic protein machinery governing diverse kinetics of calcium-evoked neurotransmitter release
    D Bose, M Bera, CA Norman, Y Timofeeva, KE Volynski, ...
    Nature communications 15 (1), 10741 , 2024
    2024
    Citations: 6
  • Plasma Membrane on a Chip
    S Ramakrishnan, RVK Sundaram, M Bera
    US Patent App. 18/409,011 , 2024
    2024
  • Synaptotagmin-1 and synaptotagmin-7 synergistically regulate the timing and plasticity of Ca2+-evoked vesicular release process
    D Bose, M Bera, CA Norman, KE Volynski, SS Krishnakumar
    Biophysical Journal 123 (3), 381a , 2024
    2024
  • Synaptophysin chaperones the assembly of 12 SNAREpins under each ready-release vesicle
    M Bera, A Radhakrishnan, J Coleman, RV K. Sundaram, S Ramakrishnan, ...
    Proceedings of the National Academy of Sciences 120 (45), e2311484120 , 2023
    2023
    Citations: 42
  • Turbocharging synaptic transmission
    JE Rothman, K Grushin, M Bera, F Pincet
    FEBS letters 597 (18), 2233-2249 , 2023
    2023
    Citations: 29
  • Roles for diacylglycerol in synaptic vesicle priming and release revealed by complete reconstitution of core protein machinery
    RV Kalyana Sundaram, A Chatterjee, M Bera, K Grushin, A Panda, F Li, ...
    Proceedings of the National Academy of Sciences 120 (34), e2309516120 , 2023
    2023
    Citations: 13
  • Rapid Quantification of First and Second Phase Insulin Secretion Dynamics using an In vitro Platform for Improving Insulin Therapy
    S Thoduvayil, JS Weerakkody, RVK Sundaram, M Topper, M Bera, ...
    Cell calcium 113, 102766 , 2023
    2023
    Citations: 2
  • K. Sundaram RV, Ramakrishnan S, Pincet F, et al. Synaptophysin chaperones the assembly of 12 SNAREpins under each ready-release vesicle
    M Bera, A Radhakrishnan, J Coleman
    Proc Natl Acad Sci USA 120, 45 , 2023
    2023
    Citations: 5
  • Native planar asymmetric suspended membrane for single‐molecule investigations: plasma membrane on a Chip
    RV Kalyana Sundaram, M Bera, J Coleman, JS Weerakkody, ...
    Small 18 (51), 2205567 , 2022
    2022
    Citations: 17
  • Molecular determinants of complexin clamping and activation function
    M Bera, S Ramakrishnan, J Coleman, SS Krishnakumar, JE Rothman
    Elife 11, e71938 , 2022
    2022
    Citations: 37
  • RETREG1/FAM134B mediated autophagosomal degradation of AMFR/GP78 and OPA1—a dual organellar turnover mechanism
    D Mookherjee, S Das, R Mukherjee, M Bera, SC Jana, S Chakrabarti, ...
    Autophagy 17 (7), 1729-1752 , 2021
    2021
    Citations: 51
  • Pulling the springs of a cell by single-molecule force spectroscopy
    C Mukherjee, M Bera, SR Koti Ainavarapu, K Sengupta
    Emerging Topics in Life Sciences 5 (1), 77-87 , 2021
    2021
    Citations: 1
  • Synergistic roles of Synaptotagmin-1 and complexin in calcium-regulated neuronal exocytosis
    S Ramakrishnan, M Bera, J Coleman, JE Rothman, SS Krishnakumar
    Elife 9, e54506 , 2020
    2020
    Citations: 63
  • Nuclear filaments: role in chromosomal positioning and gene expression
    M Bera, K Sengupta
    Nucleus 11 (1), 99-110 , 2020
    2020
    Citations: 25
  • Independent Yet Synergistic Roles of Synaptotagmin-1 and Complexin in Calcium Regulated Neuronal Exocytosis
    S Ramakrishnan, M Bera, J Coleman, JE Rothman, SS Krishnakumar
    bioRxiv, 2019.12. 16.878686 , 2019
    2019
  • Chromosome territorial organization drives efficient protein complex formation: a hypothesis
    M Bera, RVK Sundaram
    The Yale Journal of Biology and Medicine 92 (3), 541 , 2019
    2019
    Citations: 1
  • Nuclear deformation and anchorage defect induced by DCM mutants in lamin A
    M Bera, R Kumar, B Sinha, K Sengupta
    bioRxiv, 611665 , 2019
    2019
  • Synaptotagmin oligomers are necessary and can be sufficient to form a Ca 2+ ‐sensitive fusion clamp
    S Ramakrishnan, M Bera, J Coleman, SS Krishnakumar, F Pincet, ...
    FEBS letters 593 (2), 154-162 , 2019
    2019
    Citations: 55

MOST CITED SCHOLAR PUBLICATIONS

  • Synergistic roles of Synaptotagmin-1 and complexin in calcium-regulated neuronal exocytosis
    S Ramakrishnan, M Bera, J Coleman, JE Rothman, SS Krishnakumar
    Elife 9, e54506 , 2020
    2020
    Citations: 63
  • Synaptotagmin oligomers are necessary and can be sufficient to form a Ca 2+ ‐sensitive fusion clamp
    S Ramakrishnan, M Bera, J Coleman, SS Krishnakumar, F Pincet, ...
    FEBS letters 593 (2), 154-162 , 2019
    2019
    Citations: 55
  • RETREG1/FAM134B mediated autophagosomal degradation of AMFR/GP78 and OPA1—a dual organellar turnover mechanism
    D Mookherjee, S Das, R Mukherjee, M Bera, SC Jana, S Chakrabarti, ...
    Autophagy 17 (7), 1729-1752 , 2021
    2021
    Citations: 51
  • Synaptophysin chaperones the assembly of 12 SNAREpins under each ready-release vesicle
    M Bera, A Radhakrishnan, J Coleman, RV K. Sundaram, S Ramakrishnan, ...
    Proceedings of the National Academy of Sciences 120 (45), e2311484120 , 2023
    2023
    Citations: 42
  • Molecular determinants of complexin clamping and activation function
    M Bera, S Ramakrishnan, J Coleman, SS Krishnakumar, JE Rothman
    Elife 11, e71938 , 2022
    2022
    Citations: 37
  • Characterization of Unfolding Mechanism of Human Lamin A Ig Fold by Single-Molecule Force Spectroscopy Implications in EDMD
    M Bera, HC Kotamarthi, S Dutta, A Ray, S Ghosh, D Bhattacharyya, ...
    Biochemistry 53 (46), 7247-7258 , 2014
    2014
    Citations: 36
  • Turbocharging synaptic transmission
    JE Rothman, K Grushin, M Bera, F Pincet
    FEBS letters 597 (18), 2233-2249 , 2023
    2023
    Citations: 29
  • Significance of 1B and 2B domains in modulating elastic properties of lamin A
    M Bera, SRK Ainavarapu, K Sengupta
    Scientific reports 6 (1), 27879 , 2016
    2016
    Citations: 27
  • Nuclear filaments: role in chromosomal positioning and gene expression
    M Bera, K Sengupta
    Nucleus 11 (1), 99-110 , 2020
    2020
    Citations: 25
  • Native planar asymmetric suspended membrane for single‐molecule investigations: plasma membrane on a Chip
    RV Kalyana Sundaram, M Bera, J Coleman, JS Weerakkody, ...
    Small 18 (51), 2205567 , 2022
    2022
    Citations: 17
  • Roles for diacylglycerol in synaptic vesicle priming and release revealed by complete reconstitution of core protein machinery
    RV Kalyana Sundaram, A Chatterjee, M Bera, K Grushin, A Panda, F Li, ...
    Proceedings of the National Academy of Sciences 120 (34), e2309516120 , 2023
    2023
    Citations: 13
  • Two successive oligomeric Munc13 assemblies scaffold vesicle docking and SNARE assembly to support neurotransmitter release
    M Bera, K Grushin, RV Kalyana Sundaram, JS Hinzen, J Chen, ...
    Nature Communications 16 (1), 7222 , 2025
    2025
    Citations: 9
  • Minimal presynaptic protein machinery governing diverse kinetics of calcium-evoked neurotransmitter release
    D Bose, M Bera, CA Norman, Y Timofeeva, KE Volynski, ...
    Nature communications 15 (1), 10741 , 2024
    2024
    Citations: 6
  • K. Sundaram RV, Ramakrishnan S, Pincet F, et al. Synaptophysin chaperones the assembly of 12 SNAREpins under each ready-release vesicle
    M Bera, A Radhakrishnan, J Coleman
    Proc Natl Acad Sci USA 120, 45 , 2023
    2023
    Citations: 5
  • Highly stable planar asymmetric suspended membranes for investigating protein dynamics and membrane fusion
    M Bera, RV Kalyana Sundaram, J Coleman, A Chatterjee, S Thoduvayil, ...
    Nature Protocols 20 (12), 3582-3606 , 2025
    2025
    Citations: 3
  • Rapid Quantification of First and Second Phase Insulin Secretion Dynamics using an In vitro Platform for Improving Insulin Therapy
    S Thoduvayil, JS Weerakkody, RVK Sundaram, M Topper, M Bera, ...
    Cell calcium 113, 102766 , 2023
    2023
    Citations: 2
  • Günter Blobel: Pioneer of molecular cell biology (1936–2018)
    Blobel Laboratory Trainees
    Journal of Cell Biology 217 (4), 1163-1167 , 2018
    2018
    Citations: 2
  • Pulling the springs of a cell by single-molecule force spectroscopy
    C Mukherjee, M Bera, SR Koti Ainavarapu, K Sengupta
    Emerging Topics in Life Sciences 5 (1), 77-87 , 2021
    2021
    Citations: 1
  • Chromosome territorial organization drives efficient protein complex formation: a hypothesis
    M Bera, RVK Sundaram
    The Yale Journal of Biology and Medicine 92 (3), 541 , 2019
    2019
    Citations: 1
  • Plasma Membrane on a Chip
    S Ramakrishnan, RVK Sundaram, M Bera
    US Patent App. 18/409,011 , 2024
    2024