Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2828-2837 |
| Number of pages | 10 |
| Journal | Journal of Investigative Dermatology |
| Volume | 132 |
| Issue number | 12 |
| DOIs | |
| State | Published - Dec 2012 |
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ASJC Scopus subject areas
- Dermatology
- Biochemistry
- Cell Biology
- Molecular Biology
Cite this
Galectin-3 regulates intracellular trafficking of EGFR through alix and promotes keratinocyte migration. / Liu, Wei; Hsu, Daniel K.; Chen, Huan Yuan; Yang, Ri Yao; Carraway, Kermit L; Isseroff, Roslyn Rivkah; Liu, Fu-Tong.
In: Journal of Investigative Dermatology, Vol. 132, No. 12, 12.2012, p. 2828-2837.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Galectin-3 regulates intracellular trafficking of EGFR through alix and promotes keratinocyte migration
AU - Liu, Wei
AU - Hsu, Daniel K.
AU - Chen, Huan Yuan
AU - Yang, Ri Yao
AU - Carraway, Kermit L
AU - Isseroff, Roslyn Rivkah
AU - Liu, Fu-Tong
PY - 2012/12
Y1 - 2012/12
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=84870525618&partnerID=8YFLogxK
U2 - 10.1038/jid.2012.211
DO - 10.1038/jid.2012.211
M3 - Article
C2 - 22785133
AN - SCOPUS:84870525618
VL - 132
SP - 2828
EP - 2837
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
SN - 0022-202X
IS - 12
ER -