Abstract
Biogenesis of lysosome-related organelles complex-1 (BLOC-1) is a component of the molecular machinery required for the biogenesis of specialized organelles and lysosomal targeting of cargoes via the endosomal to lysosomal trafficking pathway. BLOS1, one subunit of BLOC-1, is implicated in lysosomal trafficking of membrane proteins. We found that the degradation and trafficking of epidermal growth factor receptor (EGFR) were delayed in BLOS1 knockdown cells, which were rescued through BLOS1 overexpression. A key feature to the delayed EGFR degradation is the accumulation of endolysosomes in BLOS1 knockdown cells or BLOS1 knock-out mouse embryonic fibroblasts. BLOS1 interacted with SNX2 (a retromer subunit) and TSG101 (an endosomal sorting complex required for transport subunit-I) to mediate EGFR lysosomal trafficking. These results suggest that coordination of the endolysosomal trafficking proteins is important for proper targeting of EGFR to lysosomes.
Highlights
epidermal growth factor receptor (EGFR) lysosomal trafficking process is important for the modulation of EGF signaling
We found that the degradation and trafficking of epidermal growth factor receptor (EGFR) were delayed in BLOS1 knockdown cells, which were rescued through BLOS1 overexpression
We report here that BLOS1 interacts with SNX2 and TSG101 to mediate the endolysosomal trafficking of EGFR for lysosomal degradation
Summary
EGFR lysosomal trafficking process is important for the modulation of EGF signaling. Results: Delayed EGFR degradation in BLOS1 knockdown cells is restored by the overexpressed BLOS1 fragment that interacts with both SNX2 and TSG101. BLOS1 interacted with SNX2 (a retromer subunit) and TSG101 (an endosomal sorting complex required for transport subunit-I) to mediate EGFR lysosomal trafficking. These results suggest that coordination of the endolysosomal trafficking proteins is important for proper targeting of EGFR to lysosomes. We previously reported that BLOS1 interacts with SNX1 to direct the membrane auxin efflux proteins PIN1/2 for vacuolar (or lysosomal) degradation, which could be mediated by ESCRTs in Arabidopsis [23]. We hypothesize that this pathway may be conserved in EGFR lysosomal targeting in mammalian cells. We report here that BLOS1 interacts with SNX2 and TSG101 to mediate the endolysosomal trafficking of EGFR for lysosomal degradation
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