title: MYADM regulates Rac1 targeting to ordered membranes required for cell spreading and migration.
abstract: 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.
authors.affiliation: Centro de Biología Molecular Severo Ochoa, Cantoblanco, 28049 Madrid, Spain.
authors.forename: Juan F
authors.initials: JF
authors.lastname: Aranda
authors.forename: Natalia
authors.initials: N
authors.lastname: Reglero-Real
authors.forename: Leonor
authors.initials: L
authors.lastname: Kremer
authors.forename: Beatriz
authors.initials: B
authors.lastname: Marcos-Ramiro
authors.forename: Ana
authors.initials: A
authors.lastname: Ruiz-Sáenz
authors.forename: María
authors.initials: M
authors.lastname: Calvo
authors.forename: Carlos
authors.initials: C
authors.lastname: Enrich
authors.forename: Isabel
authors.initials: I
authors.lastname: Correas
authors.forename: Jaime
authors.initials: J
authors.lastname: Millán
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Alonso
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement; D004285:Dogs; D018274:Electroporation; D005260:Female; D015870:Gene Expression; D020868:Gene Silencing; D000882:Haplorhini; D006801:Humans; D008297:Male; D021962:Membrane Microdomains / Q000378:metabolism*; D062806:Myelin and Lymphocyte-Associated Proteolipid Proteins; D010802:Phylogeny; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D014162:Transfection; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D000943:Antigens, Differentiation; C405987:MYADM protein, human; D062806:Myelin and Lymphocyte-Associated Proteolipid Proteins; D011506:Proteins; D034741:RNA, Small Interfering; D020830:rac1 GTP-Binding Protein