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WHAMM 在肾脏重吸收中发挥作用，并聚合肌动蛋白以促进自噬体膜闭合和货物隔离。

WHAMM functions in kidney reabsorption and polymerizes actin to promote autophagosomal membrane closure and cargo sequestration.

机构信息

Department of Molecular & Cell Biology, Institute for Systems Genomics, University of Connecticut, Storrs, CT 06269.

The Jackson Laboratory, Bar Harbor, ME 04609.

出版信息

Mol Biol Cell. 2024 Jun 1;35(6):ar80. doi: 10.1091/mbc.E24-01-0025. Epub 2024 Apr 10.

DOI:10.1091/mbc.E24-01-0025
PMID:38598293
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11238085/
Abstract

The actin cytoskeleton is essential for many functions of eukaryotic cells, but the factors that nucleate actin assembly are not well understood at the organismal level or in the context of disease. To explore the function of the actin nucleation factor WHAMM in mice, we examined how inactivation impacts kidney physiology and cellular proteostasis. We show that male WHAMM knockout mice excrete elevated levels of albumin, glucose, phosphate, and amino acids, and display structural abnormalities of the kidney proximal tubule, suggesting that WHAMM activity is important for nutrient reabsorption. In kidney tissue, the loss of WHAMM results in the accumulation of the lipidated autophagosomal membrane protein LC3, indicating an alteration in autophagy. In mouse fibroblasts and human proximal tubule cells, WHAMM and its binding partner the Arp2/3 complex control autophagic membrane closure and cargo receptor recruitment. These results reveal a role for WHAMM-mediated actin assembly in maintaining kidney function and promoting proper autophagosome membrane remodeling.

摘要

肌动蛋白细胞骨架对于真核细胞的许多功能至关重要，但在机体水平或疾病背景下，成核肌动蛋白组装的因素还不是很清楚。为了探究肌动蛋白成核因子 WHAMM 在小鼠中的功能，我们研究了失活如何影响肾脏生理学和细胞蛋白稳态。我们发现，雄性 WHAMM 敲除小鼠排泄的白蛋白、葡萄糖、磷酸盐和氨基酸水平升高，并且肾脏近端小管的结构异常，表明 WHAMM 活性对于营养物质的重吸收很重要。在肾脏组织中，WHAMM 的缺失导致脂化自噬体膜蛋白 LC3 的积累，表明自噬发生了改变。在小鼠成纤维细胞和人近端肾小管细胞中，WHAMM 及其结合伴侣 Arp2/3 复合物控制自噬膜闭合和货物受体募集。这些结果揭示了 WHAMM 介导的肌动蛋白组装在维持肾脏功能和促进适当的自噬体膜重塑中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c667/11238085/67b8c05e1033/mbc-35-ar80-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c667/11238085/4b3faa8bde70/mbc-35-ar80-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c667/11238085/3bc84ef23c27/mbc-35-ar80-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c667/11238085/cf372f90b673/mbc-35-ar80-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c667/11238085/c1e6abd9a6f2/mbc-35-ar80-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c667/11238085/83aa2dfd405e/mbc-35-ar80-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c667/11238085/b7547467f20a/mbc-35-ar80-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c667/11238085/d636f1958495/mbc-35-ar80-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c667/11238085/ede6ac9a7403/mbc-35-ar80-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c667/11238085/67b8c05e1033/mbc-35-ar80-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c667/11238085/4b3faa8bde70/mbc-35-ar80-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c667/11238085/3bc84ef23c27/mbc-35-ar80-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c667/11238085/cf372f90b673/mbc-35-ar80-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c667/11238085/c1e6abd9a6f2/mbc-35-ar80-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c667/11238085/83aa2dfd405e/mbc-35-ar80-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c667/11238085/b7547467f20a/mbc-35-ar80-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c667/11238085/d636f1958495/mbc-35-ar80-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c667/11238085/ede6ac9a7403/mbc-35-ar80-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c667/11238085/67b8c05e1033/mbc-35-ar80-g009.jpg

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