Author:
Gudi Radhika,Palanisamy Viswanathan,Vasu Chenthamarakshan
Abstract
AbstractCentrosomal P4.1-associated protein (CPAP) plays a critical role in restricting the centriole length in human cells. Here, we report a novel, positive regulatory role for CPAP in endocytic vesicular transport (EVT) and lysosome targeting of internalized-cell surface receptor EGFR. We observed that higher CPAP levels cause an increase in the abundance of multi-vesicular body (MVB) and EGFR is detectable in CPAP-overexpression induced puncta. While the surface levels, and total and phosphorylated cellular levels of EGFR are higher under CPAP deficiency, ligandengagement induced internalization of this receptor is not impacted by CPAP levels. Furthermore, routing of EGFR into early endosomes is not influenced by CPAP. However, most importantly, we found that CPAP is required for targeting ligand-activated, internalized EGFR to lysosome. Transport of ligand-bound EGFR from early endosome to late endosome/MVB and lysosome is severely diminished in CPAP-depleted cells. Moreover, CPAP depleted cells showed diminished ability to form MVB structures upon EGFR activation. These observations show a positive regulatory role for CPAP in early endosome to late endosome transport and lysosome targeting of ligand-bound EGFR-like cell surface receptors. Overall, identification of this regulatory role for CPAP in endocytic trafficking of EGFR provides new insights in understanding the cellular functions of CPAP.
Publisher
Cold Spring Harbor Laboratory