Galectin-3 regulates intracellular trafficking of EGFR through Alix and promotes keratinocyte migration.
The EGFR-mediated signaling pathways are important in a variety of cellular processes, including cell migration and wound re-epithelialization. Intracellular trafficking of EGFR is critical for maintaining EGFR surface expression. Galectin-3, a member of an animal lectin family, has been implicated in a number of physiological and pathological processes. Through studies of galectin-3-deficient mice and cells isolated from these mice, we demonstrated that the absence of galectin-3 impairs keratinocyte migration and skin wound re-epithelialization. We have linked this pro-migratory function to a crucial role of cytosolic galectin-3 in controlling intracellular trafficking and cell surface expression of EGFR after EGF stimulation. Without galectin-3, the surface levels of EGFR are markedly reduced, and the receptor accumulates diffusely in the cytoplasm. This is associated with reduced rates of both endocytosis and recycling of the receptor. We have provided evidence that this previously unreported function of galectin-3 may be mediated through interaction with its binding partner Alix, which is a protein component of the ESCRT (endosomal sorting complex required for transport) machinery. Our results suggest that galectin-3 is potentially a critical regulator of a number of important cellular responses through its intracellular control of trafficking of cell surface receptors.
Department of Dermatology, University of California, Davis, Davis, California 95816, USA.
Wei
W
Liu
Daniel K
DK
Hsu
Huan-Yuan
HY
Chen
Ri-Yao
RY
Yang
Kermit L
KL
Carraway
Roslyn R
RR
Isseroff
Fu-Tong
FT
Liu
D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology*; D003600:Cytosol / Q000378:metabolism; D004705:Endocytosis / Q000502:physiology; D056827:Endosomal Sorting Complexes Required for Transport / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D037502:Galectin 3 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D015603:Keratinocytes / Q000166:cytology* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D061251:Primary Cell Culture; D021381:Protein Transport / Q000502:physiology; D014945:Wound Healing / Q000502:physiology
D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D037502:Galectin 3; C485095:Lgals3 protein, mouse; C117020:PDCD6IP protein, human; C492144:Pdcd6ip protein, mouse; D066246:ErbB Receptors