Recruitment of Endophilin to Clathrin-coated Pit Necks is Required for Efficient Vesicle Uncoating After Fission

Overview

Journal Neuron

Publisher Cell Press

Specialty Neurology

Date 2011 Nov 22

PMID 22099461

Citations 185

Authors

Ira Milosevic

Silvia Giovedi

Xuelin Lou

Andrea Raimondi

Chiara Collesi

Hongying Shen

Summer Paradise

Eileen OToole

Shawn Ferguson

Ottavio Cremona

Pietro De Camilli

Affiliations

Soon will be listed here.

Abstract

Endophilin is a membrane-binding protein with curvature-generating and -sensing properties that participates in clathrin-dependent endocytosis of synaptic vesicle membranes. Endophilin also binds the GTPase dynamin and the phosphoinositide phosphatase synaptojanin and is thought to coordinate constriction of coated pits with membrane fission (via dynamin) and subsequent uncoating (via synaptojanin). We show that although synaptojanin is recruited by endophilin at bud necks before fission, the knockout of all three mouse endophilins results in the accumulation of clathrin-coated vesicles, but not of clathrin-coated pits, at synapses. The absence of endophilin impairs but does not abolish synaptic transmission and results in perinatal lethality, whereas partial endophilin absence causes severe neurological defects, including epilepsy and neurodegeneration. Our data support a model in which endophilin recruitment to coated pit necks, because of its curvature-sensing properties, primes vesicle buds for subsequent uncoating after membrane fission, without being critically required for the fission reaction itself.

Citing Articles

Synaptic sabotage: How Tau and α-Synuclein undermine synaptic health.

Uytterhoeven V, Verstreken P, Nachman E J Cell Biol. 2024; 224(2).

PMID: 39718548 PMC: 11668179. DOI: 10.1083/jcb.202409104.

Endophilin A2 Deficiency Impairs Antibody Production in Humans.

Mehawej C, Chouery E, Farah R, Khalil A, Hachem S, Corbani S J Clin Immunol. 2024; 45(1):37.

PMID: 39499372 DOI: 10.1007/s10875-024-01827-1.

A candidate loss-of-function variant in SGIP1 causes synaptic dysfunction and recessive parkinsonism.

Decet M, Scott P, Kuenen S, Meftah D, Swerts J, Calatayud C Cell Rep Med. 2024; 5(10):101749.

PMID: 39332416 PMC: 11513836. DOI: 10.1016/j.xcrm.2024.101749.

Presynaptic neurons self-tune by inversely coupling neurotransmitter release with the abundance of CaV2 voltage-gated Ca channels.

Xiong A, Richmond J, Kim H Proc Natl Acad Sci U S A. 2024; 121(35):e2404969121.

PMID: 39172783 PMC: 11363341. DOI: 10.1073/pnas.2404969121.

Parkinson's disease gene, Synaptojanin1, dysregulates the surface maintenance of the dopamine transporter.

Saenz J, Khezerlou E, Aggarwal M, Shaikh A, Ganti N, Herborg F NPJ Parkinsons Dis. 2024; 10(1):148.

PMID: 39117637 PMC: 11310474. DOI: 10.1038/s41531-024-00769-0.

References

de Heuvel E, Bell A, Ramjaun A, Wong K, Sossin W, McPherson P . Identification of the major synaptojanin-binding proteins in brain. J Biol Chem. 1997; 272(13):8710-6. DOI: 10.1074/jbc.272.13.8710. View

Frost A, Unger V, De Camilli P . The BAR domain superfamily: membrane-molding macromolecules. Cell. 2009; 137(2):191-6. PMC: 4832598. DOI: 10.1016/j.cell.2009.04.010. View

Ferguson S, Ferguson S, Raimondi A, Paradise S, Shen H, Mesaki K . Coordinated actions of actin and BAR proteins upstream of dynamin at endocytic clathrin-coated pits. Dev Cell. 2010; 17(6):811-22. PMC: 2861561. DOI: 10.1016/j.devcel.2009.11.005. View

Perera R, Zoncu R, Lucast L, De Camilli P, Toomre D . Two synaptojanin 1 isoforms are recruited to clathrin-coated pits at different stages. Proc Natl Acad Sci U S A. 2006; 103(51):19332-7. PMC: 1693868. DOI: 10.1073/pnas.0609795104. View

Sundborger A, Soderblom C, Vorontsova O, Evergren E, Hinshaw J, Shupliakov O . An endophilin-dynamin complex promotes budding of clathrin-coated vesicles during synaptic vesicle recycling. J Cell Sci. 2010; 124(Pt 1):133-43. PMC: 3001412. DOI: 10.1242/jcs.072686. View

Paolo G, De Camilli P . Phosphoinositides in cell regulation and membrane dynamics. Nature. 2006; 443(7112):651-7. DOI: 10.1038/nature05185. View

Verstreken P, Kjaerulff O, Lloyd T, Atkinson R, Zhou Y, Meinertzhagen I . Endophilin mutations block clathrin-mediated endocytosis but not neurotransmitter release. Cell. 2002; 109(1):101-12. DOI: 10.1016/s0092-8674(02)00688-8. View

Schuske K, Richmond J, Matthies D, Davis W, Runz S, Rube D . Endophilin is required for synaptic vesicle endocytosis by localizing synaptojanin. Neuron. 2003; 40(4):749-62. DOI: 10.1016/s0896-6273(03)00667-6. View

Guan R, Dai H, Han D, Harrison S, Kirchhausen T . Structure of the PTEN-like region of auxilin, a detector of clathrin-coated vesicle budding. Structure. 2010; 18(9):1191-8. PMC: 2955424. DOI: 10.1016/j.str.2010.06.016. View

10.

Antonny B . Membrane deformation by protein coats. Curr Opin Cell Biol. 2006; 18(4):386-94. DOI: 10.1016/j.ceb.2006.06.003. View

11.

Gad H, Ringstad N, Low P, Kjaerulff O, Gustafsson J, Wenk M . Fission and uncoating of synaptic clathrin-coated vesicles are perturbed by disruption of interactions with the SH3 domain of endophilin. Neuron. 2000; 27(2):301-12. DOI: 10.1016/s0896-6273(00)00038-6. View

12.

Ringstad N, Gad H, Low P, Di Paolo G, Brodin L, Shupliakov O . Endophilin/SH3p4 is required for the transition from early to late stages in clathrin-mediated synaptic vesicle endocytosis. Neuron. 2000; 24(1):143-54. DOI: 10.1016/s0896-6273(00)80828-4. View

13.

Ralser M, Nonhoff U, Albrecht M, Lengauer T, Wanker E, Lehrach H . Ataxin-2 and huntingtin interact with endophilin-A complexes to function in plastin-associated pathways. Hum Mol Genet. 2005; 14(19):2893-909. DOI: 10.1093/hmg/ddi321. View

14.

Dickman D, Horne J, Meinertzhagen I, Schwarz T . A slowed classical pathway rather than kiss-and-run mediates endocytosis at synapses lacking synaptojanin and endophilin. Cell. 2005; 123(3):521-33. DOI: 10.1016/j.cell.2005.09.026. View

15.

Cremona O, Di Paolo G, Wenk M, Luthi A, Kim W, Takei K . Essential role of phosphoinositide metabolism in synaptic vesicle recycling. Cell. 1999; 99(2):179-88. DOI: 10.1016/s0092-8674(00)81649-9. View

16.

Ringstad N, Nemoto Y, De Camilli P . The SH3p4/Sh3p8/SH3p13 protein family: binding partners for synaptojanin and dynamin via a Grb2-like Src homology 3 domain. Proc Natl Acad Sci U S A. 1997; 94(16):8569-74. PMC: 23017. DOI: 10.1073/pnas.94.16.8569. View

17.

Liu J, Sun Y, Drubin D, Oster G . The mechanochemistry of endocytosis. PLoS Biol. 2009; 7(9):e1000204. PMC: 2742711. DOI: 10.1371/journal.pbio.1000204. View

18.

Bai J, Hu Z, Dittman J, Pym E, Kaplan J . Endophilin functions as a membrane-bending molecule and is delivered to endocytic zones by exocytosis. Cell. 2010; 143(3):430-41. PMC: 2996235. DOI: 10.1016/j.cell.2010.09.024. View

19.

Madsen K, Bhatia V, Gether U, Stamou D . BAR domains, amphipathic helices and membrane-anchored proteins use the same mechanism to sense membrane curvature. FEBS Lett. 2010; 584(9):1848-55. DOI: 10.1016/j.febslet.2010.01.053. View

20.

Gallop J, Jao C, Kent H, Butler P, Evans P, Langen R . Mechanism of endophilin N-BAR domain-mediated membrane curvature. EMBO J. 2006; 25(12):2898-910. PMC: 1500843. DOI: 10.1038/sj.emboj.7601174. View