Tetraspanin CD151 promotes cell migration by regulating integrin trafficking.
Regulation of cell migration is an important feature of tetraspanin CD151. Although it is well established that CD151 physically associates with integrins, the mechanism by which CD151 regulates integrin-dependent cell migration is basically unknown. Given the fact that CD151 is localized in both the plasma membrane and intracellular vesicles, we found that CD151 and its associated alpha3beta1, alpha5beta1, and alpha6beta1 integrins undergo endocytosis and accumulate in the same intracellular vesicular compartments. CD151 contains a YRSL sequence, a YXXvarphi type of endocytosis/sorting motif, in its C-terminal cytoplasmic domain. Mutation of this motif markedly attenuated CD151 internalization. The loss of CD151 trafficking completely abrogated CD151-promoted cell migration on extracellular matrices such as laminin and diminished the internalization of its associated integrins, indicating a critical role for integrin trafficking in regulating cell motility. In conclusion, the YXXvarphi motif-mediated internalization of CD151 promotes integrin-dependent cell migration by modulating the endocytosis and/or vesicular trafficking of its associated integrins.
Liu
Li
L
Vascular Biology Center, Cancer Institute, Department of Medicine and Department of Molecular Science, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA.
He
Bo
B
Liu
Wei M
WM
Zhou
Dongming
D
Cox
John V
JV
Zhang
Xin A
XA
D000409:Alanine / Q000378:metabolism; D020816:Amino Acid Motifs / Q000235:genetics; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D003593:Cytoplasm / Q000737:chemistry; D004705:Endocytosis / Q000502:physiology; D006801:Humans; D039201:Integrin alpha3beta1 / Q000378:metabolism; D039081:Integrin alpha5beta1 / Q000378:metabolism; D039121:Integrin alpha6beta1 / Q000378:metabolism; D039564:Integrin alphaV / Q000737:chemistry / Q000378:metabolism*; D016023:Integrins / Q000378:metabolism*; D008297:Male; D051379:Mice; D041681:NIH 3T3 Cells; D011471:Prostatic Neoplasms / Q000473:pathology; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D013347:Subcellular Fractions / Q000378:metabolism; D014162:Transfection
D039201:Integrin alpha3beta1; D039081:Integrin alpha5beta1; D039121:Integrin alpha6beta1; D039564:Integrin alphaV; D016023:Integrins; D000409:Alanine