| Autor: |
Chan Wah Hak L; Institute of Structural and Molecular Biology, University College London, London, UK.; Centre for Neural Circuits and Behaviour, University of Oxford, Oxford, UK., Khan S; Institute of Structural and Molecular Biology, University College London, London, UK., Di Meglio I; Institute of Structural and Molecular Biology, University College London, London, UK.; Biochemistry Department, University of Geneva, Geneva, Switzerland., Law AL; Randall Division of Cell and Molecular Biophysics, King's College London, London, UK., Lucken-Ardjomande Häsler S; MRC Laboratory of Molecular Biology, Cambridge, UK., Quintaneiro LM; Institute of Structural and Molecular Biology, University College London, London, UK., Ferreira APA; Institute of Structural and Molecular Biology, University College London, London, UK.; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA., Krause M; Randall Division of Cell and Molecular Biophysics, King's College London, London, UK., McMahon HT; MRC Laboratory of Molecular Biology, Cambridge, UK., Boucrot E; Institute of Structural and Molecular Biology, University College London, London, UK. e.boucrot@ucl.ac.uk.; Institute of Structural and Molecular Biology, Birkbeck College, London, UK. e.boucrot@ucl.ac.uk. |
| Abstrakt: |
Endocytosis mediates the cellular uptake of micronutrients and the turnover of plasma membrane proteins. Clathrin-mediated endocytosis is the major uptake pathway in resting cells 1 , but several clathrin-independent endocytic routes exist in parallel 2,3 . One such pathway, fast endophilin-mediated endocytosis (FEME), is not constitutive but triggered upon activation of certain receptors, including the β 1 adrenergic receptor 4 . FEME activates promptly following stimulation as endophilin is pre-enriched by the phosphatidylinositol-3,4-bisphosphate-binding protein lamellipodin 4,5 . However, in the absence of stimulation, endophilin foci abort and disassemble after a few seconds. Looking for additional proteins involved in FEME, we found that 20 out of 65 BAR domain-containing proteins tested colocalized with endophilin spots. Among them, FBP17 and CIP4 prime the membrane of resting cells for FEME by recruiting the 5'-lipid phosphatase SHIP2 and lamellipodin to mediate the local production of phosphatidylinositol-3,4-bisphosphate and endophilin pre-enrichment. Membrane-bound GTP-loaded Cdc42 recruits FBP17 and CIP4, before being locally deactivated by RICH1 and SH3BP1 GTPase-activating proteins. This generates the transient assembly and disassembly of endophilin spots, which lasts 5-10 seconds. This mechanism periodically primes patches of the membrane for prompt responses upon FEME activation. |
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