Concerted regulation of focal adhesion dynamics by galectin-3 and tyrosine-phosphorylated caveolin-1.
Both tyrosine-phosphorylated caveolin-1 (pY14Cav1) and GlcNAc-transferase V (Mgat5) are linked with focal adhesions (FAs); however, their function in this context is unknown. Here, we show that galectin-3 binding to Mgat5-modified N-glycans functions together with pY14Cav1 to stabilize focal adhesion kinase (FAK) within FAs, and thereby promotes FA disassembly and turnover. Expression of the Mgat5/galectin lattice alone induces FAs and cell spreading. However, FAK stabilization in FAs also requires expression of pY14Cav1. In cells lacking the Mgat5/galectin lattice, pY14Cav1 is not sufficient to promote FAK stabilization, FA disassembly, and turnover. In human MDA-435 cancer cells, Cav1 expression, but not mutant Y14FCav1, stabilizes FAK exchange and stimulates de novo FA formation in protrusive cellular regions. Thus, transmembrane crosstalk between the galectin lattice and pY14Cav1 promotes FA turnover by stabilizing FAK within FAs defining previously unknown, interdependent roles for galectin-3 and pY14Cav1 in tumor cell migration.
Goetz
Jacky G
JG
Department of Cellular and Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada.
Joshi
Bharat
B
Lajoie
Patrick
P
Strugnell
Scott S
SS
Scudamore
Trevor
T
Kojic
Liliana D
LD
Nabi
Ivan R
IR
D000595:Amino Acid Sequence / Q000502:physiology; D000818:Animals; D051242:Caveolin 1 / Q000737:chemistry / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism* / Q000648:ultrastructure; D002465:Cell Movement / Q000502:physiology*; D003599:Cytoskeleton / Q000378:metabolism / Q000648:ultrastructure; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D022001:Focal Adhesions / Q000378:metabolism* / Q000648:ultrastructure; D037502:Galectin 3 / Q000378:metabolism*; D006801:Humans; D046911:Macromolecular Substances / Q000378:metabolism; D051379:Mice; D017351:N-Acetylglucosaminyltransferases / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000503:physiopathology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding / Q000502:physiology; D021381:Protein Transport / Q000502:physiology; D014443:Tyrosine / Q000378:metabolism
D051242:Caveolin 1; D037502:Galectin 3; D046911:Macromolecular Substances; D009419:Nerve Tissue Proteins; D014443:Tyrosine; C479741:MGAT5B protein, human; D017351:N-Acetylglucosaminyltransferases; D051416:Focal Adhesion Protein-Tyrosine Kinases