What is Fast Endophilin-Mediated Endocytosis (FEME)? 2018-02-05T16:48:26+00:00

What is Fast Endophilin-Mediated Endocytosis (FEME)?

FEME is a novel clathrin-independent endocytic pathway, regulated by the BAR domain protein endophilin, where tubulo-vesicular carriers form within seconds at the plasma membrane upon activation of specific G-protein coupled receptors (GPCRs) by their ligands, internalizing GPCRs and moving rapidly towards the perinucleolar area [1]. FEME requires PI3K signaling, where class 1 PI3K, upon receptor activation, phosphorylates phosphatidylinositol-4,5-bisphosphate (PtdIns (4,5)P2 or PIP2), producing PIP3.

fast-endophilin-mediated-endocytosis-feme

FEME is a novel clathrin-independent endocytic pathway, regulated by the BAR domain protein endophilin and is regulated by PI3K signaling.

The rapid dephosphorylation of PIP3 back into PIP2 by the SHIP phosphatases recruits lamellipodin at the leading edge of migrating cells, which subsequently binds endophilin. This accumulation of endophilin induces the FEME pathway [1]. Endophilin alone performs 3 distinct functions in this pathway: its SH3 domain binds to cargo receptors, its BAR domain induces membrane curvature and its multiple membrane helices supports membrane scission in co-operation with dynamin and actin. This pathway is hijacked by bacterial Shiga and cholera toxins for infection, demonstrated by endophilin coating tubule-shaped membrane invaginations that arise when Shiga toxin B binds to the cell membrane [2].

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  1. Boucrot E, Ferreira APA, Almeida-Souza L, Debard S, Vallis Y, Howard G, Bertot L, Sauvonnet N, and McMahon HT. Endophilin marks and controls a clathrin-independent endocytic pathway. Nature 2014; 517(7535):460-5. [PMID: 25517094]
  2. Renard H, Simunovic M, Lemière J, Boucrot E, Garcia-Castillo MD, Arumugam S, Chambon V, Lamaze C, Wunder C, Kenworthy AK, Schmidt AA, McMahon HT, Sykes C, Bassereau P, and Johannes L. Endophilin-A2 functions in membrane scission in clathrin-independent endocytosis. Nature 2014; 517(7535):493-6. [PMID: 25517096]