Raver1 interactions with vinculin and RNA suggest a feed-forward pathway in directing mRNA to focal adhesions.
The translational machinery of the cell relocalizes to focal adhesions following the activation of integrin receptors. This response allows for rapid, local production of components needed for adhesion complex assembly and signaling. Vinculin links focal adhesions to the actin cytoskeleton following its activation by integrin signaling, which severs intramolecular interactions of vinculin's head and tail (Vt) domains. Our vinculin:raver1 crystal structures and binding studies show that activated Vt selectively interacts with one of the three RNA recognition motifs of raver1, that the vinculin:raver1 complex binds to F-actin, and that raver1 binds selectively to RNA, including a sequence found in vinculin mRNA. Further, mutation of residues that mediate interaction of raver1 with vinculin abolish their colocalization in cells. These findings suggest a feed-forward model where vinculin activation at focal adhesions provides a scaffold for recruitment of raver1 and its mRNA cargo to facilitate the production of components of adhesion complexes.
Lee
Jun Hyuck
JH
Cell Adhesion Laboratory, Department of Cancer Biology, The Scripps Research Institute, Jupiter, FL 33458, USA.
Rangarajan
Erumbi S
ES
Yogesha
S D
SD
Izard
Tina
T
D000199:Actins / Q000378:metabolism; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology; D017124:Conserved Sequence; D003460:Crystallization; D003599:Cytoskeleton / Q000378:metabolism; D022001:Focal Adhesions / Q000502:physiology*; D005822:Genetic Vectors; D006367:HeLa Cells; D006801:Humans; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012313:RNA / Q000378:metabolism*; D012333:RNA, Messenger / Q000737:chemistry / Q000378:metabolism*; D012261:Ribonucleoproteins; D017386:Sequence Homology, Amino Acid; D055672:Static Electricity; D014162:Transfection; D016596:Vinculin / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*
D000199:Actins; D002352:Carrier Proteins; D009687:Nuclear Proteins; C486705:RAVER1 protein, human; D012333:RNA, Messenger; D012261:Ribonucleoproteins; D016596:Vinculin; D012313:RNA