Liquid-Liquid Phase Separation in Neuronal Development and Synaptic Signaling

Acuna, 2016, How to make an active zone: unexpected universal functional redundancy between RIMs and RIM-BPs, Neuron, 91, 792, 10.1016/j.neuron.2016.07.042 Alabi, 2012, Synaptic vesicle pools and dynamics, Cold Spring Harbor Perspect. Biol., 4, a013680, 10.1101/cshperspect.a013680 Araki, 2015, Rapid dispersion of SynGAP from synaptic spines triggers AMPA receptor insertion and spine enlargement during LTP, Neuron, 85, 173, 10.1016/j.neuron.2014.12.023 Banani, 2017, Biomolecular condensates: organizers of cellular biochemistry, Nat. Rev. Mol. Cell Biol., 18, 285, 10.1038/nrm.2017.7 Benton, 2003, A conserved oligomerization domain in Drosophila Bazooka/PAR-3 is important for apical localization and epithelial polarity, Curr. Biol., 13, 1330, 10.1016/S0960-9822(03)00508-6 Bergstralh, 2017, Spindle orientation: a question of complex positioning, Development, 144, 1137, 10.1242/dev.140764 Berry, 2017, Spine dynamics: are they all the same?, Neuron, 96, 43, 10.1016/j.neuron.2017.08.008 Beutel, 2019, Phase separation of zonula occludens proteins drives formation of tight junctions, Cell, 179, 923, 10.1016/j.cell.2019.10.011 Biederer, 2017, Transcellular nanoalignment of synaptic function, Neuron, 96, 680, 10.1016/j.neuron.2017.10.006 Bowman, 2006, The Drosophila NuMa Homolog Mud regulates spindle orientation in asymmetric cell division, Dev. Cell, 10, 731, 10.1016/j.devcel.2006.05.005 Brangwynne, 2009, Germline P granules are liquid droplets that localize by controlled dissolution/condensation, Science, 324, 1729, 10.1126/science.1172046 Brangwynne, 2011, Active liquid-like behavior of nucleoli determines their size and shape in Xenopus laevis oocytes, Proc. Natl. Acad. Sci. USA, 108, 4334, 10.1073/pnas.1017150108 Chen, 1998, A synaptic Ras-GTPase activating protein (p135 SynGAP) inhibited by CaM kinase II, Neuron, 20, 895, 10.1016/S0896-6273(00)80471-7 Chen, 2020, Phase separation at the synapse, Nat. Neurosci., 23, 301, 10.1038/s41593-019-0579-9 Choksi, 2006, Prospero acts as a binary switch between self-renewal and differentiation in Drosophila neural stem cells, Dev. Cell, 11, 775, 10.1016/j.devcel.2006.09.015 Chuang, 2018, Amyloid assembly and disassembly, J. Cell Sci., 131, 10.1242/jcs.189928 de Vivo, 2017, Ultrastructural evidence for synaptic scaling across the wake/sleep cycle, Science, 355, 507, 10.1126/science.aah5982 di Pietro, 2016, Regulation of mitotic spindle orientation: an integrated view, EMBO Rep, 17, 1106, 10.15252/embr.201642292 Diering, 2017, Homer1a drives homeostatic scaling-down of excitatory synapses during sleep, Science, 355, 511, 10.1126/science.aai8355 Doe, 2017, Temporal patterning in the Drosophila CNS, Annu. Rev. Cell Dev. Biol., 33, 219, 10.1146/annurev-cellbio-111315-125210 Doe, 1991, The Prospero gene specifies cell fates in the Drosophila central nervous system, Cell, 65, 451, 10.1016/0092-8674(91)90463-9 Erben, 2008, Asymmetric localization of the adaptor protein Miranda in neuroblasts is achieved by diffusion and sequential interaction of myosin II and VI, J. Cell Sci., 121, 1403, 10.1242/jcs.020024 Etemad-Moghadam, 1995, Asymmetrically distributed PAR-3 protein contributes to cell polarity and spindle alignment in early C. elegans embryos, Cell, 83, 743, 10.1016/0092-8674(95)90187-6 Fanning, 2009, Zonula occludens-1 and -2 are cytosolic scaffolds that regulate the assembly of cellular junctions, Ann. N. Y. Acad. Sci., 1165, 113, 10.1111/j.1749-6632.2009.04440.x Feng, 2007, The Par-3 NTD adopts a PB1-like structure required for Par-3 oligomerization and membrane localization, EMBO J, 26, 2786, 10.1038/sj.emboj.7601702 Feng, 2009, Organization and dynamics of PDZ-domain-related supramodules in the postsynaptic density, Nat. Rev. Neurosci., 10, 87, 10.1038/nrn2540 Feng, 2019, Formation of biological condensates via phase separation: characteristics, analytical methods, and physiological implications, J. Biol. Chem., 294, 14823, 10.1074/jbc.REV119.007895 Fujioka, 2020, Phase separation organizes the site of autophagosome formation, Nature, 578, 301, 10.1038/s41586-020-1977-6 Goehring, 2014, PAR polarity: from complexity to design principles, Exp. Cell Res., 328, 258, 10.1016/j.yexcr.2014.08.009 Goehring, 2011, PAR proteins diffuse freely across the anterior-posterior boundary in polarized C. elegans embryos, J. Cell Biol., 193, 583, 10.1083/jcb.201011094 Goldstein, 2007, The PAR proteins: fundamental players in animal cell polarization, Dev. Cell, 13, 609, 10.1016/j.devcel.2007.10.007 Gönczy, 2008, Mechanisms of asymmetric cell division: flies and worms pave the way, Nat. Rev. Mol. Cell Biol., 9, 355, 10.1038/nrm2388 Han, 2012, Cell-free formation of RNA granules: bound RNAs identify features and components of cellular assemblies, Cell, 149, 768, 10.1016/j.cell.2012.04.016 Hirano, 2005, Structure of a cell polarity regulator, a complex between atypical PKC and Par6 PB1 domains, J. Biol. Chem., 280, 9653, 10.1074/jbc.M409823200 Holguera, 2018, Neuronal specification in space and time, Science, 362, 176, 10.1126/science.aas9435 Holly, 2020, A conserved PDZ-binding motif in aPKC interacts with Par-3 and mediates cortical polarity, Curr. Biol., 30, 893, 10.1016/j.cub.2019.12.055 Huganir, 2013, AMPARs and synaptic plasticity: the last 25 years, Neuron, 80, 704, 10.1016/j.neuron.2013.10.025 Hung, 1999, PAR-6 is a conserved PDZ domain-containing protein that colocalizes with PAR-3 in Caenorhabditis elegans embryos, Development, 126, 127, 10.1242/dev.126.1.127 Ikeshima-Kataoka, 1997, Miranda directs Prospero to a daughter cell during Drosophila asymmetric divisions, Nature, 390, 625, 10.1038/37641 Izumi, 1998, An atypical PKC directly associates and colocalizes at the epithelial tight junction with ASIP, a mammalian homologue of Caenorhabditis elegans polarity protein PAR-3, J. Cell Biol., 143, 95, 10.1083/jcb.143.1.95 Joberty, 2000, The cell-polarity protein Par6 links Par3 and atypical protein kinase C to Cdc42, Nat. Cell Biol., 2, 531, 10.1038/35019573 Kato, 2012, Cell-free formation of RNA granules: low complexity sequence domains form dynamic fibers within hydrogels, Cell, 149, 753, 10.1016/j.cell.2012.04.017 Kim, 1997, GKAP, a novel synaptic protein that interacts with the guanylate kinase-like domain of the PSD-95/SAP90 family of channel clustering molecules, J. Cell Biol., 136, 669, 10.1083/jcb.136.3.669 Kim, 2013, Mutations in prion-like domains in hnRNPA2B1 and hnRNPA1 cause multisystem proteinopathy and ALS, Nature, 495, 467, 10.1038/nature11922 Kim, 1998, SynGAP: a synaptic RasGAP that associates with the PSD-95/SAP90 protein family, Neuron, 20, 683, 10.1016/S0896-6273(00)81008-9 Knoblich, 2010, Asymmetric cell division: recent developments and their implications for tumour biology, Nat. Rev. Mol. Cell Biol., 11, 849, 10.1038/nrm3010 Kono, 2019, Reconstruction of Par-dependent polarity in apolar cells reveals a dynamic process of cortical polarization, eLife, 8, e45559, 10.7554/eLife.45559 Kornau, 1995, Domain interaction between NMDA receptor subunits and the postsynaptic density protein Psd-95, Science, 269, 1737, 10.1126/science.7569905 Kriegstein, 2009, The glial nature of embryonic and adult neural stem cells, Annu. Rev. Neurosci., 32, 149, 10.1146/annurev.neuro.051508.135600 Kuchinke, 1998, Control of spindle orientation in Drosophila by the Par-3-related PDZ-domain protein Bazooka, Curr. Biol., 8, 1357, 10.1016/S0960-9822(98)00016-5 Lang, 2017, The PAR proteins: from molecular circuits to dynamic self-stabilizing cell polarity, Development, 144, 3405, 10.1242/dev.139063 Li, 2012, Phase transitions in the assembly of multivalent signalling proteins, Nature, 483, 336, 10.1038/nature10879 Liao, 2019, RNA granules hitchhike on lysosomes for long-distance transport, using annexin A11 as a molecular tether, Cell, 179, 147, 10.1016/j.cell.2019.08.050 Lin, 2000, A mammalian PAR-3-PAR-6 complex implicated in Cdc42/Rac1 and aPKC signalling and cell polarity, Nat. Cell Biol., 2, 540, 10.1038/35019582 Lin, 2015, Formation and maturation of phase-separated liquid droplets by RNA-binding proteins, Mol. Cell, 60, 208, 10.1016/j.molcel.2015.08.018 Liu, 2020, Mitotic implantation of the transcription factor Prospero via phase separation drives terminal neuronal differentiation, Dev. Cell, 52, 277, 10.1016/j.devcel.2019.11.019 Liu, 2020, Par complex cluster formation mediated by phase separation, Nat. Commun., 11, 2266, 10.1038/s41467-020-16135-6 Lu, 1999, Modes of protein movement that lead to the asymmetric localization of partner of numb during Drosophila neuroblast division, Mol. Cell, 4, 883, 10.1016/S1097-2765(00)80218-X Lu, 1998, Partner of numb colocalizes with numb during mitosis and directs numb asymmetric localization in Drosophila neural and muscle progenitors, Cell, 95, 225, 10.1016/S0092-8674(00)81753-5 Ma, 2018, A membraneless organelle associated with the endoplasmic reticulum enables 3′UTR-mediated protein-protein interactions, Cell, 175, 1492, 10.1016/j.cell.2018.10.007 Mayer, 2005, Quantitative analysis of protein dynamics during asymmetric cell division, Curr. Biol., 15, 1847, 10.1016/j.cub.2005.08.067 Milovanovic, 2017, Synaptic vesicle clusters at synapses: a distinct liquid phase?, Neuron, 93, 995, 10.1016/j.neuron.2017.02.013 Milovanovic, 2018, A liquid phase of synapsin and lipid vesicles, Science, 361, 604, 10.1126/science.aat5671 Molliex, 2015, Phase separation by low complexity domains promotes stress granule assembly and drives pathological fibrillization, Cell, 163, 123, 10.1016/j.cell.2015.09.015 Murakami, 2015, ALS/FTD mutation-induced phase transition of FUS liquid droplets and reversible hydrogels into irreversible hydrogels impairs RNP granule function, Neuron, 88, 678, 10.1016/j.neuron.2015.10.030 Naisbitt, 1999, Shank, a novel family of postsynaptic density proteins that binds to the NMDA receptor/PSD-95/GKAP complex and cortactin, Neuron, 23, 569, 10.1016/S0896-6273(00)80809-0 Nedelsky, 2019, Bridging biophysics and neurology: aberrant phase transitions in neurodegenerative disease, Nat. Rev. Neurol., 15, 272, 10.1038/s41582-019-0157-5 Nicoll, 2006, Auxiliary subunits assist AMPA-type glutamate receptors, Science, 311, 1253, 10.1126/science.1123339 Nishiyama, 2015, Biochemical computation for spine structural plasticity, Neuron, 87, 63, 10.1016/j.neuron.2015.05.043 Ohtsuka, 2002, Cast: a novel protein of the cytomatrix at the active zone of synapses that forms a ternary complex with RIM1 and munc13-1, J. Cell Biol., 158, 577, 10.1083/jcb.200202083 Pak, 2016, Sequence determinants of intracellular phase separation by complex coacervation of a disordered protein, Mol. Cell, 63, 72, 10.1016/j.molcel.2016.05.042 Patel, 2015, A liquid-to-solid phase transition of the ALS protein FUS accelerated by disease mutation, Cell, 162, 1066, 10.1016/j.cell.2015.07.047 Pechstein, 2020, Vesicle clustering in a living synapse depends on a synapsin region that mediates phase separation, Cell Rep, 30, 2594, 10.1016/j.celrep.2020.01.092 Pieribone, 1995, Distinct pools of synaptic vesicles in neurotransmitter release, Nature, 375, 493, 10.1038/375493a0 Rhyu, 1994, Asymmetric distribution of numb protein during division of the sensory organ precursor cell confers distinct fates to daughter cells, Cell, 76, 477, 10.1016/0092-8674(94)90112-0 Rodriguez-Boulan, 2014, Organization and execution of the epithelial polarity programme, Nat. Rev. Mol. Cell Biol., 15, 225, 10.1038/nrm3775 Rosahl, 1995, Essential functions of synapsins I and II in synaptic vesicle regulation, Nature, 375, 488, 10.1038/375488a0 Ryan, 2019, Physiological, pathological, and targetable membraneless organelles in neurons, Trends Neurosci, 42, 693, 10.1016/j.tins.2019.08.005 Schaefer, 2000, A protein complex containing Inscuteable and the Gα-binding protein Pins orients asymmetric cell divisions in Drosophila, Curr. Biol., 10, 353, 10.1016/S0960-9822(00)00401-2 Schwayer, 2019, Mechanosensation of tight junctions depends on ZO-1 phase separation and flow, Cell, 179, 937, 10.1016/j.cell.2019.10.006 Shan, 2018, Basal condensation of Numb and Pon complex via phase transition during Drosophila neuroblast asymmetric division, Nat. Commun., 9, 737, 10.1038/s41467-018-03077-3 Shen, 1997, Miranda is required for the asymmetric localization of Prospero during mitosis in Drosophila, Cell, 90, 449, 10.1016/S0092-8674(00)80505-X Sheng, 2007, The postsynaptic architecture of excitatory synapses: a more quantitative view, Annu. Rev. Biochem., 76, 823, 10.1146/annurev.biochem.76.060805.160029 Shin, 2017, Liquid phase condensation in cell physiology and disease, Science, 357, eaaf4382, 10.1126/science.aaf4382 Silbereis, 2016, The cellular and molecular landscapes of the developing human central nervous system, Neuron, 89, 248, 10.1016/j.neuron.2015.12.008 Siller, 2009, Spindle orientation during asymmetric cell division, Nat. Cell Biol., 11, 365, 10.1038/ncb0409-365 St George-Hyslop, 2018, The physiological and pathological biophysics of phase separation and gelation of RNA binding proteins in amyotrophic lateral sclerosis and fronto-temporal lobar degeneration, Brain Res, 1693, 11, 10.1016/j.brainres.2018.04.036 St Johnston, 2018, Establishing and transducing cell polarity: common themes and variations, Curr. Opin. Cell Biol., 51, 33, 10.1016/j.ceb.2017.10.007 Stevenson, 1986, Identification of ZO-1: a high molecular weight polypeptide associated with the tight junction (zonula occludens) in a variety of epithelia, J. Cell Biol., 103, 755, 10.1083/jcb.103.3.755 Su, 2016, Phase separation of signaling molecules promotes T cell receptor signal transduction, Science, 352, 595, 10.1126/science.aad9964 Südhof, 2012, The presynaptic active zone, Neuron, 75, 11, 10.1016/j.neuron.2012.06.012 Südhof, 2017, Synaptic neurexin complexes: a molecular code for the logic of neural circuits, Cell, 171, 745, 10.1016/j.cell.2017.10.024 Südhof, 2018, Towards an understanding of synapse formation, Neuron, 100, 276, 10.1016/j.neuron.2018.09.040 Sugiyama, 2005, Determination of absolute protein numbers in single synapses by a GFP-based calibration technique, Nat. Methods, 2, 677, 10.1038/nmeth783 Tabuse, 1998, Atypical protein kinase C cooperates with PAR-3 to establish embryonic polarity in Caenorhabditis elegans, Development, 125, 3607, 10.1242/dev.125.18.3607 Takamori, 2006, Molecular anatomy of a trafficking organelle, Cell, 127, 831, 10.1016/j.cell.2006.10.030 Tang, 2016, A trans-synaptic nanocolumn aligns neurotransmitter release to receptors, Nature, 536, 210, 10.1038/nature19058 Taverna, 2014, The cell biology of neurogenesis: toward an understanding of the development and evolution of the neocortex, Annu. Rev. Cell Dev. Biol., 30, 465, 10.1146/annurev-cellbio-101011-155801 Uemura, 1989, numb, a gene required in determination of cell fate during sensory organ formation in Drosophila embryos, Cell, 58, 349, 10.1016/0092-8674(89)90849-0 Umeda, 2006, ZO-1 and ZO-2 independently determine where claudins are polymerized in tight-junction strand formation, Cell, 126, 741, 10.1016/j.cell.2006.06.043 Venkei, 2018, Emerging mechanisms of asymmetric stem cell division, J. Cell Biol., 217, 3785, 10.1083/jcb.201807037 Wang, 2012, Substrate recognition mechanism of atypical protein kinase Cs revealed by the structure of PKCiota in complex with a substrate peptide from Par-3, Structure, 20, 791, 10.1016/j.str.2012.02.022 Wang, 2018, A molecular grammar governing the driving forces for phase separation of prion-like RNA binding proteins, Cell, 174, 688, 10.1016/j.cell.2018.06.006 Wang, 2016, Fusion competent synaptic vesicles persist upon active zone disruption and loss of vesicle docking, Neuron, 91, 777, 10.1016/j.neuron.2016.07.005 Wang, 1997, Rim is a putative Rab3 effector in regulating synaptic-vesicle fusion, Nature, 388, 593, 10.1038/41580 Wang, 2000, The RIM/NIM family of neuronal C2 domain proteins. Interactions with Rab3 and a new class of Src homology 3 domain proteins, J. Biol. Chem., 275, 20033, 10.1074/jbc.M909008199 Wen, 2018, Protein complex assemblies in epithelial cell polarity and asymmetric cell division, J. Mol. Biol., 430, 3504, 10.1016/j.jmb.2017.09.013 Wodarz, 2000, Drosophila atypical protein kinase C associates with Bazooka and controls polarity of epithelia and neuroblasts, J. Cell Biol., 150, 1361, 10.1083/jcb.150.6.1361 Wolozin, 2019, Stress granules and neurodegeneration, Nat. Rev. Neurosci., 20, 649, 10.1038/s41583-019-0222-5 Wu, 2019, RIM and RIM-BP form presynaptic active-zone-like condensates via phase separation, Mol. Cell, 73, 971, 10.1016/j.molcel.2018.12.007 Xiao, 1998, Homer regulates the association of group 1 metabotropic glutamate receptors with multivalent complexes of homer-related, synaptic proteins, Neuron, 21, 707, 10.1016/S0896-6273(00)80588-7 Yamasaki, 2020, Liquidity is a critical determinant for selective autophagy of protein condensates, Mol. Cell, 77, 1163, 10.1016/j.molcel.2019.12.026 Yu, 2000, Analysis of partner of inscuteable, a novel player of Drosophila asymmetric divisions, reveals two distinct steps in inscuteable apical localization, Cell, 100, 399, 10.1016/S0092-8674(00)80676-5 Zeng, 2018, Reconstituted postsynaptic density as a molecular platform for understanding synapse formation and plasticity, Cell, 174, 1172, 10.1016/j.cell.2018.06.047 Zeng, 2019, Phase separation-mediated TARP/MAGUK complex condensation and AMPA receptor synaptic transmission, Neuron, 104, 529, 10.1016/j.neuron.2019.08.001 Zeng, 2016, Phase transition in postsynaptic densities underlies formation of synaptic complexes and synaptic plasticity, Cell, 166, 1163, 10.1016/j.cell.2016.07.008 Zhu, 2016, Mechanistic basis of MAGUK-organized complexes in synaptic development and signalling, Nat. Rev. Neurosci., 17, 209, 10.1038/nrn.2016.18