{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T21:05:25Z","timestamp":1791407125322,"version":"4.3.3"},"reference-count":53,"publisher":"Rockefeller University Press","issue":"5","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2000,9,4]]},"abstract":"<jats:p>We find that profilin contributes in several ways to Cdc42-induced nucleation of actin filaments in high speed supernatant of lysed neutrophils. Depletion of profilin inhibited Cdc42-induced nucleation; re-addition of profilin restored much of the activity. Mutant profilins with a decreased affinity for either actin or poly-l-proline were less effective at restoring activity. Whereas Cdc42 must activate Wiskott-Aldrich Syndrome protein (WASP) to stimulate nucleation by the Arp2\/3 complex, VCA (verpolin homology, cofilin, and acidic domain contained in the COOH-terminal fragment of N-WASP) constitutively activates the Arp2\/3 complex. Nucleation by VCA was not inhibited by profilin depletion. With purified N-WASP and Arp2\/3 complex, Cdc42-induced nucleation did not require profilin but was enhanced by profilin, wild-type profilin being more effective than mutant profilin with reduced affinity for poly-l-proline.<\/jats:p>\n                  <jats:p>Nucleation by the Arp2\/3 complex is a function of the free G-actin concentration. Thus, when profilin addition decreased the free G-actin concentration, it inhibited Cdc42- and VCA-induced nucleation. However, when profilin was added with G-actin in a ratio that maintained the initial free G-actin concentration, it increased the rate of both Cdc42- and VCA-induced nucleation. This enhancement, also seen with purified proteins, was greatest when the free G-actin concentration was low. These data suggest that under conditions present in intact cells, profilin enhances nucleation by activated Arp2\/3 complex.<\/jats:p>","DOI":"10.1083\/jcb.150.5.1001","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T12:45:41Z","timestamp":1027687541000},"page":"1001-1012","update-policy":"https:\/\/doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":108,"title":["Profilin Enhances Cdc42-Induced Nucleation of Actin Polymerization"],"prefix":"10.1083","volume":"150","author":[{"given":"Changsong","family":"Yang","sequence":"first","affiliation":[{"name":"aDepartment of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6018"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minzhou","family":"Huang","sequence":"additional","affiliation":[{"name":"aDepartment of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6018"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"DeBiasio","sequence":"additional","affiliation":[{"name":"aDepartment of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6018"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Pring","sequence":"additional","affiliation":[{"name":"bDepartment of Physiology, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6018"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Joyce","sequence":"additional","affiliation":[{"name":"aDepartment of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6018"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Miki","sequence":"additional","affiliation":[{"name":"cDepartment of Biochemistry, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadaomi","family":"Takenawa","sequence":"additional","affiliation":[{"name":"cDepartment of Biochemistry, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sally H.","family":"Zigmond","sequence":"additional","affiliation":[{"name":"aDepartment of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6018"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2000,9,5]]},"reference":[{"key":"2023072902395338900_Abdul-Mananetal1999","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1038\/20726","article-title":"Structure of Cdc42 in complex with the GTPase-binding domain of the Wiskott-Aldrich syndrome protein","volume":"399","author":"Abdul-Manan","year":"1999","journal-title":"Nature"},{"key":"2023072902395338900_Baninetal1996","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1016\/S0960-9822(02)00642-5","article-title":"Wiskott-Aldrich syndrome protein (WASp) is a binding partner for c-Src family protein-tyrosine kinases","volume":"6","author":"Banin","year":"1996","journal-title":"Curr. 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