Netrin-1 stimulated axon growth requires the polyglutamylase TTLL1 DOI Creative Commons
Kyle R. Northington,

J. L. CALDERON,

Emily Anne Bates

и другие.

Frontiers in Neuroscience, Год журнала: 2024, Номер 18

Опубликована: Окт. 14, 2024

Introduction In the developing brain, neurons extend an axonal process through a complex and changing environment to form synaptic connections with correct targets in response extracellular cues. Microtubule actin filaments provide mechanical support drive axon growth direction. The cytoskeleton responds guidance Netrin-1 is multifunctional cue that can induce alternate responses based on bound receptor. mechanism by which well described. However, how influences microtubule less understood. Appropriate function required for pathfinding, as mutations tubulin phenocopy crossing defects of DCC mutants. stabilization attractive response. C-terminal tails microtubules be post-translationally modified. Post-translational modifications (PTMs) help control cytoskeleton. Methods We measured polyglutamylation cultured primary mouse cortical before after stimulation. used immunohistochemistry measure stimulation alters microtubule-associated protein localization. Next, we manipulated TTLL1 determine if Netrin-1-induced MAP localization depend levels. Results this study, investigated signaling PTMs axon. found increases This change necessary rate increases. next determined MAP1B DCX changes Netrin-1. These proteins both stabilize may responsible neurons. TTLL1, polyglutamylation.

Язык: Английский

Microtubule-associated protein MAP7 promotes tubulin posttranslational modifications and cargo transport to enable osmotic adaptation DOI
Yusheng Shen, Kassandra M Ori-McKenney

Developmental Cell, Год журнала: 2024, Номер 59(12), С. 1553 - 1570.e7

Опубликована: Апрель 3, 2024

Язык: Английский

Процитировано

13
More is different: Reconstituting complexity in microtubule regulation DOI Creative Commons
Elizabeth J. Lawrence, Saptarshi Chatterjee, Marija Žanić

и другие.

Journal of Biological Chemistry, Год журнала: 2023, Номер 299(12), С. 105398 - 105398

Опубликована: Окт. 28, 2023

Microtubules are dynamic cytoskeletal filaments that undergo stochastic switching between phases of polymerization and depolymerization—a behavior known as instability. Many important cellular processes, including cell motility, chromosome segregation, intracellular transport, require complex spatiotemporal regulation microtubule dynamics. This coordinated is achieved through the interactions numerous microtubule-associated proteins (MAPs) with ends lattices. Here, we review recent advances in our understanding regulation, focusing on results arising from biochemical vitro reconstitution approaches using purified multiprotein ensembles. We discuss how combinatory effects MAPs affect both dynamics individual ends, well stability turnover lattice. In addition, highlight new demonstrating roles protein condensates regulation. Our overall intent to showcase lessons learned help unravel regulatory mechanisms at play environments. crucial for a variety division, transport. Their hollow cylindrical structures typically composed 13 protofilaments assembled αβ-tubulin heterodimers, α-tubulin subunits exposed minus end β-tubulin plus end. Microtubule stochastically switch growth shrinkage process instability (1Mitchison T. Kirschner M. Dynamic growth.Nature. 1984; 312: 237-242Crossref PubMed Google Scholar). nonequilibrium process, powered by GTPase activity tubulin. Tubulin heterodimers incorporate into polymer GTP bound their subunits, which subsequently hydrolyzes, resulting lattice predominantly GDP-β-tubulin. However, since hydrolysis occurs delay, growing maintains structurally distinct stabilizing 'cap' GTP-tubulin its It loss regaining this cap transition (known 'catastrophe') 'rescue'). regulated complex, interconnected network (MAPs). Individual modulate rates frequencies catastrophe rescue. Due number complexity among regulators within cells, it challenging dissect specific functions microtubules. To circumvent this, bottom-up reductionist essential—where one starts minimal components, deciphers nature consequence those progressively enhances increasing components controlled fashion. The core philosophy underlying approach reverse-engineer cell–biological environment outside (2Liu A.P. Fletcher D.A. Biology under construction: function.Nat. Rev. Mol. Cell Biol. 2009; 10: 644-650Crossref Scopus (173) microtubule-based phenomena cells originated purification tubulin ability assemble microtubules (3Borisy G.G. Olmsted J.B. Marcum J.M. Allen C. assembly vitro.Fed. Proc. 1974; 33: 167-174PubMed Scholar, 4Lee J.C. Timasheff S.N. Reconstitution calf brain tubulin.Biochemistry. 1975; 14: 5183-5187Crossref (0) 5Weisenberg R.C. formation solutions containing low calcium concentrations.Science. 1972; 177: 1104-1105Crossref Scholar), led discovery Shortly thereafter, reconstituted was directly visualized level video-enhanced differential interference contrast microscopy (6Horio Hotani H. Visualization dark-field microscopy.Nature. 1986; 321: 605-607Crossref 7Walker R.A. O'Brien E.T. Pryer N.K. Soboeiro M.F. Voter W.A. Erickson H.P. et al.Dynamic analyzed video light microscopy: rate constants frequencies.J. 1988; 107: 1437-1448Crossref (811) Concurrently early efforts, catalog were being discovered characterized 8Cleveland D.W. Hwo S.Y. M.W. Purification tau, induces tubulin.J. 1977; 116: 207-225Crossref (734) 9Sloboda R.D. Rudolph S.A. Rosenbaum J.L. Greengard P. Cyclic AMP-dependent endogenous phosphorylation protein.Proc. Natl. Acad. Sci. U. S. A. 72: 177-181Crossref Although landmark advancements field provided fundamental insights dynamics, there caveat—the parameters observed different than cells. discrepancies observations brought center stage studies clear pathway probing cytoskeleton (10Kinoshita K. Arnal I. Desai Drechsel D.N. Hyman A.A. physiological components.Science. 2001; 294: 1340Crossref (184) Since then, enormous progress has been made combinations MAPs. review, lattices key (Fig. 1), an interplay acting concert 1). Several autonomously bind ends. For example, EB-family recognize (11Maurer S.P. Fourniol F.J. Bohner G. Moores C.A. Surrey EBs nucleotide-dependent structural ends.Cell. 2012; 149: 371-382Abstract Full Text PDF (278) 12Zanic Stear J.H. Howard J. EB1 recognizes nucleotide state lattice.PLoS One. 4e7585Crossref (119) 13Zhang R. Alushin G.M.M. Brown Nogales E. Mechanistic origin modulation EB proteins.Cell. 2015; 162: 849-859Abstract Xenopus 215 (XMAP215)-family use highly conserved tubulin-binding tumor overexpressed gene domains dimers regardless (14Al-Bassam Kim Flor-Parra Lal N. Velji Chang F. Fission yeast Alp14 dose-dependent end–tracking polymerase.Mol. Cell. 23: 2878-2890Crossref 15Al-Bassam Regulation TOG-domain XMAP215/Dis1 CLASP.Trends 2011; 21: 604-614Abstract (177) 16Brouhard G.J. Noetzel T.L. Al-Bassam Kinoshita Harrison S.C. al.XMAP215 processive polymerase.Cell. 2008; 132: 79-88Abstract (404) 17Brouhard Rice L.M. dynamics: biochemistry mechanics.Nat. 2018; 19: 451-463Crossref (292) 18Farmer V.J. Zanic proteins.Curr. 2021; 31: R499-R501Abstract 19Gard D.L. Becker B.E. Josh Romney MAPping eukaryotic tree life: structure, function, evolution MAP215⧸Dis1 family proteins.Int. Cytol. 2004; 239: 179-272Crossref 20Slep K.C. role TOG dynamics.Biochem. Soc. Trans. 37: 1002-1006Crossref (44) 21Slep Vale Structural basis tracking XMAP215, CLIP-170, EB1.Mol. 2007; 27: 976-991Abstract (197) 22Van Breugel D. Stu2p, budding member Dis1/XMAP215 end-binding destabilizer.J. 2003; 161: 359-369Crossref (104) Notably, recruit additional plus-end-tracking (+TIPs) act conjunction (23Akhmanova Steinmetz M.O. +TIPs glance.J. 2010; 123: 3415-3419Crossref (211) Indeed, many contain SxIP amino acid sequence motif, specifically recognized homology domain serves end-localization signal 'hitchhiking' (24Honnappa Okhrimenko O. Jaussi Jawhari Jelesarov Winkler F.K. al.Key interaction modes +TIP networks.Mol. 2006; 663-671Abstract (148) 25Honnappa Gouveia S.M. Weisbrich Damberger F.F. Bhavesh N.S. al.An EB1-binding motif acts tip localization signal.Cell. 138: 366-376Abstract (504) 26Kumar Wittmann +TIPs: SxIPping along ends.Trends 22: 418-428Abstract (98) Other prominent +TIPs, such cytoplasmic linker 170 kDa (CLIP-170), via direct CAP-Gly C-terminal EEY (27Bieling Kandels-Lewis Telley I.A. Van Dijk Janke CLIP-170 tracks dynamically recognizing composite EB1/tubulinbinding sites.J. 183: 1223-1233Crossref 28Dixit Barnett B. Lazarus J.E. Tokito Goldman Y.E. Holzbaur E.L.F. plus-end requires EB1.Proc. 106: 492-497Crossref (154) 29Galjart CLIPs CLASPs dynamics.Nat. 2005; 6: 487-498Crossref (164) Thus, GTP-cap, interact other MAPs, multivalency these all facilitate higher-order complexes years, investigated combinatorial paying particular attention EBs. vitro, strongly promoting (30Bieling Laan L. Schek Munteanu E.L. Sandblad Dogterom al.Reconstitution system vitro.Nature. 450: 1100-1105Crossref (373) 31Komarova Y. Groot C.O.D. Grigoriev Schober al.Mammalian binding control persistent growth.J. 184: 691-706Crossref (297) 32Vitre Coquelle F.M. Heichette Garnier Chrétien regulates sheet closure vitro.Nat. 415-421Crossref (203) strikingly altered when combined +TIPs. kinesin-13 mitotic centromere-associated kinesin (MCAK), potent depolymerase spindle organization dividing contains facilitates (25Honnappa 33Cooper J.R. Wagenbach Asbury C.L. Wordeman Catalysis on-rate major parameter regulating MCAK.Nat. Struct. 17: 77-83Crossref (71) 34Desai Verma Mitchison T.J. Walczak C.E. Kin I kinesins microtubule-destabilizing enzymes.Cell. 1999; 96: 69-78Abstract (597) 35Gardner M.K. Gell Bormuth V. Depolymerizing Kip3 MCAK shape architecture catastrophe.Cell. 147: 1092-1103Abstract (169) 36Helenius Brouhard Kalaidzidis Diez depolymerizing uses diffusion rapidly target ends.Nature. 441: 115-119Crossref (367) 37Hunter A.W. Caplow Coy Hancock W.O. al.The kinesin-related forms ATP-hydrolyzing ends.Mol. 11: 445-457Abstract 38Moores Milligan Lucky - depolymerisation motors.J. 119: 3905-3913Crossref 39Walczak XKCM1: during assembly.Cell. 1996; 84: 37-47Abstract (466) 40Wordeman Microtubule-depolymerizing kinesins.Curr. Opin. 82-88Crossref (95) EB-dependent targeting MCAK's destabilizing (41Montenegro Leslie Kapitein L.C. Buey R.M. al.In functional EB3 ends.Curr. 20: 1717-1722Abstract (117) linker-associated (CLASP) CLASPs' motifs provides another example amplified due (42Aher Kok Sharma Rai Olieric Rodriguez-Garcia al.CLASP suppresses catastrophes single domain.Dev. 46: 40-58.e8Abstract (65) 43Lawrence E.J. Arpag Norris S.R. Human CLASP2 rescue.Mol. 29: 1168-1177Crossref (51) 44Mimori-Kiyosue Lansbergen Sasaki Matsui Severin al.CLASP1 regulate cortex.J. 168: 141-153Crossref (329) gene-domain migration, neuronal development (15Al-Bassam 45Akhmanova Hoogenraad C.C. Drabek Stepanova Dortland Verkerk al.Clasps CLIP-115 -170 associating involved regional motile fibroblasts.Cell. 104: 923-935Abstract (402) 46Lawrence 2020; 133: jcs243097Crossref (17) On own, stabilize suppressing rescue—these dramatically enhanced CLASP targeted 47Al-Bassam van Oijen promotes rescue recruiting microtubule.Dev. 245-258Abstract (153) 48Lawrence Chatterjee pre-catastrophe intermediate shrinkage.J. 2023; 222e202107027Crossref (2) 49Lawrence Rescuing brink catastrophe: lead way.Curr. 2019; 56: 94-101Crossref (18) 50Majumdar Chen Z. Munyoki Tso Brautigam isolated 1359-1375Crossref (26) 51Slep A symphony: owed TOG.Dev. 5-7Abstract Interestingly, presence EB, protects against Such synergistic antagonistic underscore nuanced balance EB-mediated Reconstitutions multi-MAP ensembles pave way recapitulating cellular-like vitro. grow significantly faster more frequently compared polymerized similar concentrations study demonstrated several characteristics can be recapitulated three-component module tubulin, XKCM1 (the homolog MCAK) XMAP215 accelerated growth, while simultaneously induced frequent events. XMAP215's polymerase relies preferred stabilization weakly bound, curved (52Ayaz Ye X. Huddleston TOG:alphabeta-tubulin structure reveals conformation-based polymerase.Science. 337: 857-860Crossref (171) 53Ayaz Geyer E.A. Piedra F.-A. Vu E.S. Bromberg al.A tethered delivery mechanism explains catalytic action polymerase.Elife. 2014; 3e03069Crossref (81) increases order magnitude (16Brouhard 54Farmer Arpağ Hall S.L. disrupting end.J. 220e202012144Crossref (16) 55Gard eggs plus-end.J. 1987; 105: 2203-2215Crossref 56Vasquez R.J. Gard Cassimeris XMAP rapid turnover.J. 1994; 127: 985-993Crossref (188) 57Zanic Widlund P.O. Synergy levels.Nat. 2013; 15: 688-693Crossref (114) Combining leads further, acceleration bringing highest levels (57Zanic allosteric, do not directly. Rather, straightening likely release incorporated dimer, allowing quickly subsequent incoming dimer (13Zhang also suggested form Sentin, +TIP, promote cooperative (58Li W. Moriwaki Tani Watanabe Kaibuchi Goshima Drosophila EB1, Sentin.J. 199: 849-862Crossref (45) Sentin exhibits XMAP215-dependent best knowledge, established. whether EB1–Sentin–XMAP215 These findings need proteins, have parse apart allosteric (through microtubule) mediated formation. addition fast catastrophes, periods pausing recurrent events (59Brittle A.L. Ohkura Mini spindles, homologue, interphase Drosophila.EMBO 24: 1387-1396Crossref (68) 60Sousa Reis Sampaio Sunkel Mast/Orbit behaviour pause state.Cell Motil. Cytoskeleton. 64: 605-620Crossref (43) 61Trogden K.P. Rogers spatially Rac-GSK3beta dynamics.PLoS 10e0138966Crossref (9) behaviors exhibited grown alone nor XKCM1/MCAK (7Walker 10Kinoshita combination melanogaster homologs five MAPs: MCAK, (62Moriwaki Five factors reconstitute three dynamics.J. 2016; 215: 357-368Crossref (37) resulted rescues, pausing, thus reconstituting main collective restricted increased focus biochemically exhibit minus-end particularly acentrosomal arrays, differentiated epithelial, neuronal, muscle cortical arrays plants (63Akhmanova minus-end-targeting 25: PR162-R171Abstract 64Akhmanova jcs227850Crossref (7) 65Martin Akhmanova Coming focus: organization.Trends 28: 574-588Abstract Calmodulin-regulated spectrin-associated (CAMSAPs) essential noncentrosomal epithelial (66Atherton Jiang Stangier M.M. Luo Hua Houben model recognition protection CAMSAP proteins.Nat. 2017; 931-943Crossref 67Goodwin S.S. Patronin protecting 143: 263-274Abstract (191) 68Hendershott M.C. CAMSAPs Patronin.Proc. 111: 5860-5865Crossref 69Jiang Mohan Yau K.W. Liu Q. al.Microtubule polymerization-driven deposition.Dev. 295-309Abstract 70Tanaka Meng Nagae Takeichi Nezha/CAMSAP3 CAMSAP2 cooperate epithelial-specific orga

Язык: Английский

Процитировано

6
Measurements of neurite extension and nucleokinesis in an iPSC-derived model system following microtubule perturbation DOI Creative Commons
Muriel Sébastien, Alexandra Paquette,

Lilian Ferotin

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Фев. 7, 2024

In neurons, patterns of different microtubule types are essential for neurite extension and nucleokinesis. Cellular model systems such as rodent primary cultures induced pluripotent stem cells (iPSC)-derived neurons have provided key insights into how these created maintained through the action microtubule-associated proteins (MAPs), motor proteins, regulatory enzymes. iPSC-derived models show tremendous promise but lack benchmarking validation relative to cultures. Here we characterized a recent model, in which doxycycline-induced expression Neurogenin-2 drives consistent trans-differentiation neuronal state (EBiSC-NEUR1 referred NGN2 below). We developed suite open-access, semi-automated methods measure nucleokinesis compare favorably published data from other models. Then, challenged with panel drugs that perturb physiology. were significantly perturbed by two microtubule-targeting drugs, namely taxane (paclitaxel) vinca alkaloid (DZ-2384). contrast, inhibition severing (spastazoline) or deacetylation (trichostatin A) had limited effect on only. Our results support importance dynamics development demonstrate power system.

Язык: Английский

Процитировано

0
Netrin-1 stimulated axon growth requires the polyglutamylase TTLL1 DOI Creative Commons
Kyle R. Northington,

J. L. CALDERON,

Emily Anne Bates

и другие.

Frontiers in Neuroscience, Год журнала: 2024, Номер 18

Опубликована: Окт. 14, 2024

Introduction In the developing brain, neurons extend an axonal process through a complex and changing environment to form synaptic connections with correct targets in response extracellular cues. Microtubule actin filaments provide mechanical support drive axon growth direction. The cytoskeleton responds guidance Netrin-1 is multifunctional cue that can induce alternate responses based on bound receptor. mechanism by which well described. However, how influences microtubule less understood. Appropriate function required for pathfinding, as mutations tubulin phenocopy crossing defects of DCC mutants. stabilization attractive response. C-terminal tails microtubules be post-translationally modified. Post-translational modifications (PTMs) help control cytoskeleton. Methods We measured polyglutamylation cultured primary mouse cortical before after stimulation. used immunohistochemistry measure stimulation alters microtubule-associated protein localization. Next, we manipulated TTLL1 determine if Netrin-1-induced MAP localization depend levels. Results this study, investigated signaling PTMs axon. found increases This change necessary rate increases. next determined MAP1B DCX changes Netrin-1. These proteins both stabilize may responsible neurons. TTLL1, polyglutamylation.

Язык: Английский

Процитировано

0