PMID- 21325632 OWN - NLM STAT- MEDLINE DCOM- 20110816 LR - 20211020 IS - 1939-4586 (Electronic) IS - 1059-1524 (Print) IS - 1059-1524 (Linking) VI - 22 IP - 8 DP - 2011 Apr 15 TI - MYADM regulates Rac1 targeting to ordered membranes required for cell spreading and migration. PG - 1252-62 LID - 10.1091/mbc.E10-11-0910 [doi] AB - Membrane organization into condensed domains or rafts provides molecular platforms for selective recruitment of proteins. Cell migration is a general process that requires spatiotemporal targeting of Rac1 to membrane rafts. The protein machinery responsible for making rafts competent to recruit Rac1 remains elusive. Some members of the MAL family of proteins are involved in specialized processes dependent on this type of membrane. Because condensed membrane domains are a general feature of the plasma membrane of all mammalian cells, we hypothesized that MAL family members with ubiquitous expression and plasma membrane distribution could be involved in the organization of membranes for cell migration. We show that myeloid-associated differentiation marker (MYADM), a protein with unique features within the MAL family, colocalizes with Rac1 in membrane protrusions at the cell surface and distributes in condensed membranes. MYADM knockdown (KD) cells had altered membrane condensation and showed deficient incorporation of Rac1 to membrane raft fractions and, similar to Rac1 KD cells, exhibited reduced cell spreading and migration. Results of rescue-of-function experiments by expression of MYADM or active Rac1L61 in cells knocked down for Rac1 or MYADM, respectively, are consistent with the idea that MYADM and Rac1 act on parallel pathways that lead to similar functional outcomes. FAU - Aranda, Juan F AU - Aranda JF AD - Centro de Biologia Molecular Severo Ochoa, Cantoblanco, 28049 Madrid, Spain. FAU - Reglero-Real, Natalia AU - Reglero-Real N FAU - Kremer, Leonor AU - Kremer L FAU - Marcos-Ramiro, Beatriz AU - Marcos-Ramiro B FAU - Ruiz-Saenz, Ana AU - Ruiz-Saenz A FAU - Calvo, Maria AU - Calvo M FAU - Enrich, Carlos AU - Enrich C FAU - Correas, Isabel AU - Correas I FAU - Millan, Jaime AU - Millan J FAU - Alonso, Miguel A AU - Alonso MA LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110216 PL - United States TA - Mol Biol Cell JT - Molecular biology of the cell JID - 9201390 RN - 0 (Antigens, Differentiation) RN - 0 (MYADM protein, human) RN - 0 (Myelin and Lymphocyte-Associated Proteolipid Proteins) RN - 0 (Proteins) RN - 0 (RNA, Small Interfering) RN - EC 3.6.5.2 (rac1 GTP-Binding Protein) SB - IM MH - Animals MH - Antigens, Differentiation/genetics/*metabolism MH - Cell Adhesion MH - Cell Line, Tumor MH - Cell Membrane/metabolism MH - *Cell Movement MH - Dogs MH - Electroporation MH - Female MH - Gene Expression MH - Gene Silencing MH - Haplorhini MH - Humans MH - Male MH - Membrane Microdomains/*metabolism MH - Myelin and Lymphocyte-Associated Proteolipid Proteins MH - Phylogeny MH - Proteins/genetics/*metabolism MH - RNA, Small Interfering/metabolism MH - Transfection MH - rac1 GTP-Binding Protein/genetics/*metabolism PMC - PMC3078064 EDAT- 2011/02/18 06:00 MHDA- 2011/08/17 06:00 PMCR- 2011/06/30 CRDT- 2011/02/18 06:00 PHST- 2011/02/18 06:00 [entrez] PHST- 2011/02/18 06:00 [pubmed] PHST- 2011/08/17 06:00 [medline] PHST- 2011/06/30 00:00 [pmc-release] AID - mbc.E10-11-0910 [pii] AID - E10-11-0910 [pii] AID - 10.1091/mbc.E10-11-0910 [doi] PST - ppublish SO - Mol Biol Cell. 2011 Apr 15;22(8):1252-62. doi: 10.1091/mbc.E10-11-0910. Epub 2011 Feb 16.