FCHo proteins bind nascent clathrin-coated pit

Stable Identifier
R-HSA-8862280
Type
Reaction
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
Summation

Stabilization of the transient binding of AP-2 and clathrin at the plasma membrane is effected by the recruitment of a number of early acting proteins, including FCHo (F-BAR domain-containing Fer/Cip4 homology domain-only) proteins 1 and 2, intersectins (ITSNs), EPS15, EPS15L1, REPS1 and SGIP1 among others (Henne et al, 2010; Stimpson et al, 2009; Reider et al, 2009; Dergai et al, 2010; Antonescu et al, 2011; reviewed in McMahon and Boucrot, 2011).

FCHo proteins interact with the plasma membrane-enriched PI(4,5)P2 through the F-BAR domain, which recognizes curvature in the membrane (Henne et al, 2010; Henne et al, 2007; Shimada et al, 2007; Umasankar et al, 2012). Other F-BAR proteins, such as FNBP1 and FNBP1L may join the nascent clathrin-coated pit at a slightly later stage (Shimada et al, 2007). Recruitment of EPS15 and ITSN1 and 2 appears coincident with binding of FCHo2 and depends on direct interaction with the AP2 mu homology domain of FCHo2 (Henne et al, 2010).


SGIP1 (Src homology 3-domain growth factor receptor-bound 2-like (endophilin) interacting protein 1) interacts with numerous endocytic proteins including AP-2, ITSN1, REPS1, EPS15, endophilin and amphiphsyin1 and is thought to play a role in clathrin-mediated endocytosis (Trevaskis et al, 2005; Dergai et al, 2010; Uezu et al, 2007). SGIP1 is related to the FCHo proteins and is co-immunoprecipitated in a tripartite complex containing ITSN1 and REPS1 (Dergai et al, 2010). The exact function of SGIP1 in clathrin-mediated endocytosis remains to be elucidated, however recent work suggests SGIP1 and FCHo proteins may contribute to allosteric changes in AP-2 that promote membrane binding and cargo recognition (Hollopeter et al, 2014).


The recruitment of this group of early CCP proteins is rapidly followed by the incorporation of many AP-2 and clathrin molecules, stimulated in part by the FCHo- and SGIP-dependent stabilization of the open, membrane binding conformation of AP-2 (Hollopeter et al, 2014). Alternately, a proportion of the nascent CCPs may undergo abortive initiation (Loerke et al, 2009; Aguet et al, 2013; Antonescu et al, 2011). This is prompted in part through the early recruitment of the 170 kDa isoform of synaptojanin 1 (SYNJ1-170, not shown in this reaction). SYNJ1 catalyzes the hydrolysis of PI(4,5)P2 to PI(4)P and destabilizes the interaction of many early CCP components with the plasma membrane (Perera et al, 2006).

Literature References
PubMed ID Title Journal Year
17540576 Structure and analysis of FCHo2 F-BAR domain: a dimerizing and membrane recruitment module that effects membrane curvature Structure 2007
17512409 Curved EFC/F-BAR-domain dimers are joined end to end into a filament for membrane invagination in endocytosis Cell 2007
21779028 Molecular mechanism and physiological functions of clathrin-mediated endocytosis Nat. Rev. Mol. Cell Biol. 2011
22484487 Distinct and separable activities of the endocytic clathrin-coat components Fcho1/2 and AP-2 in developmental patterning Nat. Cell Biol. 2012
19296720 Cargo and dynamin regulate clathrin-coated pit maturation PLoS Biol. 2009
20448150 FCHo proteins are nucleators of clathrin-mediated endocytosis Science 2010
23891661 Advances in analysis of low signal-to-noise images link dynamin and AP2 to the functions of an endocytic checkpoint Dev. Cell 2013
21613550 Phosphatidylinositol-(4,5)-bisphosphate regulates clathrin-coated pit initiation, stabilization, and size Mol. Biol. Cell 2011
19776351 Early-arriving Syp1p and Ede1p function in endocytic site placement and formation in budding yeast Mol. Biol. Cell 2009
25303366 The membrane-associated proteins FCHo and SGIP are allosteric activators of the AP2 clathrin adaptor complex Elife 2014
20946875 Intersectin 1 forms complexes with SGIP1 and Reps1 in clathrin-coated pits Biochem. Biophys. Res. Commun. 2010
17158794 Two synaptojanin 1 isoforms are recruited to clathrin-coated pits at different stages Proc. Natl. Acad. Sci. U.S.A. 2006
19713939 Syp1 is a conserved endocytic adaptor that contains domains involved in cargo selection and membrane tubulation EMBO J. 2009
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