{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T02:04:05Z","timestamp":1791597845114,"version":"4.3.4"},"reference-count":53,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2007,4,25]],"date-time":"2007-04-25T00:00:00Z","timestamp":1177459200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Traffic"],"published-print":{"date-parts":[[2007,6]]},"abstract":"<jats:p><jats:bold>Glycosyl\u2010phosphatidylinositol (GPI)\u2010anchored proteins (GPI\u2010APs) are present at the surface of living cells in cholesterol dependent nanoscale clusters. These clusters appear to act as sorting signals for the selective endocytosis of GPI\u2010APs via a Cdc42\u2010regulated, dynamin and clathrin\u2010independent pinocytic pathway called the GPI\u2010AP\u2010enriched early endosomal compartments<\/jats:bold> (<jats:bold>GEECs) pathway. Here we show that endocytosis via the GEECs pathway is inhibited by mild depletion of cholesterol, perturbation of actin polymerization or overexpression of the Cdc42\/Rac\u2010interactive\u2010binding (CRIB) motif of neural Wiskott\u2212Aldrich syndrome protein (N\u2010WASP). Consistent with the involvement of Cdc42\u2010based actin nanomachinery, nascent endocytic vesicles containing cargo for the GEEC pathway co\u2010localize with fluorescent protein\u2010tagged isoforms of Cdc42, CRIB domain, N\u2010WASP and actin; high\u2010resolution electron microscopy on plasma membrane sheets reveals Cdc42\u2010labelled regions rich in green fluorescent protein\u2013GPI. Using total internal reflection fluorescence microscopy at the single\u2010molecule scale, we find that mild cholesterol depletion alters the dynamics of actin polymerization at the cell surface by inhibiting Cdc42 activation and consequently its stabilization at the cell surface. These results suggest that endocytosis into GEECs occurs through a cholesterol\u2010sensitive, Cdc42\u2010based recruitment of the actin polymerization machinery.<\/jats:bold><\/jats:p>","DOI":"10.1111\/j.1600-0854.2007.00565.x","type":"journal-article","created":{"date-parts":[[2007,5,6]],"date-time":"2007-05-06T16:29:07Z","timestamp":1178468947000},"page":"702-717","source":"Crossref","is-referenced-by-count":180,"title":["Cholesterol\u2010Sensitive Cdc42 Activation Regulates Actin Polymerization for Endocytosis via the GEEC Pathway"],"prefix":"10.1111","volume":"8","author":[{"given":"Rahul","family":"Chadda","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark T.","family":"Howes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah J.","family":"Plowman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John F.","family":"Hancock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert G.","family":"Parton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satyajit","family":"Mayor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2007,4,25]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01451"},{"key":"e_1_2_6_3_2","first-page":"759","volume-title":"Endocytosis. 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