دورية أكاديمية
Centrosomal P4.1-associated protein (CPAP) positively regulates endocytic vesicular transport and lysosome targeting of EGFR.
العنوان: | Centrosomal P4.1-associated protein (CPAP) positively regulates endocytic vesicular transport and lysosome targeting of EGFR. |
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المؤلفون: | Gudi R; Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, 29425, USA. gudi@musc.edu., Palanisamy V; Department of Biochemistry, Medical University of South Carolina, Charleston, SC, 29425, USA., Vasu C; Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, 29425, USA. vasu@musc.edu. |
المصدر: | Scientific reports [Sci Rep] 2021 Jun 16; Vol. 11 (1), pp. 12689. Date of Electronic Publication: 2021 Jun 16. |
نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: London : Nature Publishing Group, copyright 2011- |
مواضيع طبية MeSH: | Lysosomes/*metabolism , Microtubule-Associated Proteins/*metabolism , Transport Vesicles/*metabolism, Cell Line, Tumor ; Endocytosis ; Endosomes/metabolism ; ErbB Receptors/metabolism ; HEK293 Cells ; HeLa Cells ; Humans ; Ligands ; Microtubule-Associated Proteins/genetics ; Multivesicular Bodies/metabolism ; Protein Transport |
مستخلص: | Centrosomal P4.1-associated protein (CPAP) plays a critical role in restricting the centriole length in human cells. Here, we report a novel, positive regulatory influence for CPAP on 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. The surface and cellular levels of EGFR are higher under CPAP deficiency and lower under CPAP overexpression. While ligand-engagement induced internalization or routing of EGFR into early endosomes is not influenced by cellular levels of CPAP, we found that targeting of ligand-activated, internalized EGFR to lysosome is impacted by CPAP levels. Transport of ligand-bound EGFR from early endosome to late endosome/MVB and lysosome is diminished in CPAP-depleted cells. Moreover, CPAP depleted cells appear to show a diminished ability to form MVB structures upon EGFR activation. These observations suggest a positive regulatory effect of CPAP on EVT of ligand-bound EGFR-like cell surface receptors to MVB and lysosome. Overall, identification of a non-centriolar function of CPAP in endocytic trafficking provides new insights in understanding the non-canonical cellular functions of CPAP. |
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معلومات مُعتمدة: | P30 CA138313 United States CA NCI NIH HHS; R21 DE026965 United States DE NIDCR NIH HHS; S10 OD018113 United States OD NIH HHS |
المشرفين على المادة: | 0 (CENPJ protein, human) 0 (Ligands) 0 (Microtubule-Associated Proteins) EC 2.7.10.1 (EGFR protein, human) EC 2.7.10.1 (ErbB Receptors) |
تواريخ الأحداث: | Date Created: 20210617 Date Completed: 20211029 Latest Revision: 20240505 |
رمز التحديث: | 20240505 |
مُعرف محوري في PubMed: | PMC8209166 |
DOI: | 10.1038/s41598-021-91818-8 |
PMID: | 34135376 |
قاعدة البيانات: | MEDLINE |
تدمد: | 2045-2322 |
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DOI: | 10.1038/s41598-021-91818-8 |