Reactome: A Curated Pathway Database

Endophilins recruit synaptojanins to the clathrin-coated pit

Stable Identifier
Homo sapiens
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Synaptojanin (SYNJ) 1 and 2 are inositol-5-phosphatases that sequentially convert PI(4,5)P2 to PI(4)P and PI (Cremona et al 1999; reviewed in Billcliff and Lowe, 2014). Conversion of PI(4,5)P2 to PI(4)P and PI accompanies maturation of the clathrin-coated pit, and consistent with this, SYNJ proteins are recruited to the clathrin-coated pit through interactions with a number of endocytic proteins including ITSNs, EPS15, PACSIN proteins and endophilins, as well as with clathrin and AP-2 (Haffner et al, 1997; Cestra et al, 1999; Maire et al, 2004; Schuske et al, 2003; Verstreken et al, 2003; Modregger et al, 2000; Perera et al 2006; Milosevic et al, 2011; reviewed in Dittman and Ryan, 2009). SYJN1 exists in two isoforms, a longer 170 kDA isoform and a shorter 145 kDA isoform, with slightly different roles. The recruitment and activity of SYNJ1-145 appears to largely coincide with that of dynamin at later stages of vesicle formation, while the SYNJ1-170 isoform also plays earlier roles in stabilizing the growing clathrin-coated vesicle (Perera et al, 2006; Taylor et al, 2011; Antonescu et al, 2011). SYNJ-mediated hydrolysis of PI(4,5)P2 to PI(4)P is most efficient on highly curved, endophilin-coated tubules of the vesicle neck and contributes to dynamin-mediated membrane scission (Chang-Ileto et al, 2011; reviewed in Daumke et al, 2014; McMahon and Boucrot, 2011).

In addition to SYNJ1 and 2, other inositol-5-phosphatases are also recruited to the CCP at the time of scission. These include OCRL, which is recruited through interaction with clathrin as well as the RAB5 interactor APPL1 (Erdmann et al, 2007; Mao et al, 2009; Taylor et al, 2011; Nandez et al, 2014).

Literature References
PubMed ID Title Journal Year
10542231 The SH3 domains of endophilin and amphiphysin bind to the proline-rich region of synaptojanin 1 at distinct sites that display an unconventional binding specificity J. Biol. Chem. 1999
21779028 Molecular mechanism and physiological functions of clathrin-mediated endocytosis Nat. Rev. Mol. Cell Biol. 2011
24966051 Inositol lipid phosphatases in membrane trafficking and human disease Biochem. J. 2014
19536138 A PH domain within OCRL bridges clathrin-mediated membrane trafficking to phosphoinositide metabolism EMBO J. 2009
19575674 Molecular circuitry of endocytosis at nerve terminals Annu. Rev. Cell Dev. Biol. 2009
14622578 Synaptojanin is recruited by endophilin to promote synaptic vesicle uncoating Neuron 2003
10535736 Essential role of phosphoinositide metabolism in synaptic vesicle recycling Cell 1999
11082044 All three PACSIN isoforms bind to endocytic proteins and inhibit endocytosis J. Cell. Sci. 2000
9428629 Synaptojanin 1: localization on coated endocytic intermediates in nerve terminals and interaction of its 170 kDa isoform with Eps15 FEBS Lett 1997
14622579 Endophilin is required for synaptic vesicle endocytosis by localizing synaptojanin Neuron 2003
21613550 Phosphatidylinositol-(4,5)-bisphosphate regulates clathrin-coated pit initiation, stabilization, and size Mol. Biol. Cell 2011
25107275 A role of OCRL in clathrin-coated pit dynamics and uncoating revealed by studies of Lowe syndrome cells Elife 2014
17765681 A role of the Lowe syndrome protein OCRL in early steps of the endocytic pathway Dev. Cell 2007
22099461 Recruitment of endophilin to clathrin-coated pit necks is required for efficient vesicle uncoating after fission Neuron 2011
24581490 BAR domain scaffolds in dynamin-mediated membrane fission Cell 2014
21445324 A high precision survey of the molecular dynamics of mammalian clathrin-mediated endocytosis PLoS Biol. 2011
17158794 Two synaptojanin 1 isoforms are recruited to clathrin-coated pits at different stages Proc. Natl. Acad. Sci. U.S.A. 2006
15260957 Dap160/intersectin scaffolds the periactive zone to achieve high-fidelity endocytosis and normal synaptic growth Neuron 2004
21316588 Synaptojanin 1-mediated PI(4,5)P2 hydrolysis is modulated by membrane curvature and facilitates membrane fission Dev. Cell 2011
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