Abstract
Motility requires protrusive activity at the cellular edge, where Rho family members regulate actin dynamics. Here we show that p95-APP1 (ArfGAP-putative, Pix-interacting, paxillin-interacting protein 1), a member of the GIT1/PKL family, is part of a complex that interacts with Rac. Wild-type and truncated p95-APP1 induce actin-rich protrusions mediated by Rac and ADP-ribosylation factor 6 (Arf6). Distinct p95-APP1-derived polypeptides have different distributions, indicating that p95-APP1 cycles between the cell surface and endosomes. Our results show that p95-APP1 functionally interacts with Rac and localizes to endosomal compartments, thus identifying p95-APP1 as a molecular link between actin organization, adhesion, and membrane transport during cell motility.
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Acknowledgements
We are grateful to B. Ranscht for the E13 chick-brain cDNA library, to E. Manser and L. Lim for the pXJ40–HA–βPIX plasmid and the anti-PIX antibody, to V. Hsu for the anti-Arf6 antibody, to G. Bokoch for the pCMV6m/Pak1 plasmid and the anti-Pak1 antibody, and to J. Meldolesi for critical reading of the manuscript. The financial support of Telethon-Italy (grant n.1171 to I.d.C.) is gratefully acknowledged. A.D.C. was supported by a fellowship from the Armenise-Harvard Foundation. C.A. was supported by a fellowship from the Italian Federation for Cancer Research (FIRC).
Correspondence and requests for materials should be addressed to I.d.C. The nucleotide sequence of p95-APP1 has been deposited at Genbank under accession number AF216970.
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Di Cesare, A., Paris, S., Albertinazzi, C. et al. p95-APP1 links membrane transport to Rac-mediated reorganization of actin . Nat Cell Biol 2, 521–530 (2000). https://doi.org/10.1038/35019561
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DOI: https://doi.org/10.1038/35019561
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