CK2 involvement in ESCRT-III complex phosphorylation

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• 作者：Mauro Salvi^a ; ^{mauro.salvi@unipd.it" class="auth_mail} ; Camilla Raiborg^b ; Phyllis I. Hanson^c ; Coen Campsteijn^b ; Harald Stenmark^b ; Lorenzo A. Pinna^a ; ^d ; ^e
• 关键词：Protein kinase CK2 ; ESCRT ; CHMP2B ; CHMP3 ; VPS4
• 刊名：Archives of Biochemistry and Biophysics
• 出版年：1 March, 2014
• 年：2014
• 卷：545
• 期：Complete
• 页码：83-91
• 全文大小：2543 K

文摘

The multivesicular body (MVB) sorting pathway is a mechanism for delivering transmembrane proteins into the lumen of the lysosome for degradation. ESCRT-III is the final complex in the pathway that assembles on endosomes and executes membrane scission of intraluminal vesicles. In addition, proteins of this complex are involved in other topologically similar processes such as cytokinesis, virus egress and autophagy. Here we show that protein kinase CK2伪 is involved in the phosphorylation of the ESCRT-III subunits CHMP3 and CHMP2B, as well as of VPS4B/SKD1, an ATPase that mediates ESCRT-III disassembly. This phosphorylation is observed both in vitro and in cells. While we do not observe recruitment of CK2伪 to endosomes, we demonstrate the localization of CK2伪 to midbodies during cytokinesis. Phosphomimetic and non-phosphorylatable mutants of ESCRT-III proteins can still bind endosomes and localize to midbodies, indicating that CK2伪 does not regulate ESCRT-III localization. Finally, we analyzed two cellular functions where CHMP3, CHMP2B and VPS4 are known to be involved, epidermal growth factor degradation and cytokinetic abscission. We demonstrate that the former is impaired by CK2伪 downregulation whereas the latter is not affected. Taken together, our results indicate that CK2伪 regulates the function of ESCRT-III proteins in MVB sorting.