PXD036242-1

PXD036242 is an original dataset announced via ProteomeXchange.

Title	PIK3C3/VPS34 controls Sertoli cell polarity in the mouse testis through the stabilization of the actin cytoskeleton
Description	Sertoli cells are highly polarized testicular cells that provide a nurturing environment for germ cell development and maturation during spermatogenesis. The Class III PI3K, PIK3C3/VPS34 plays key roles in endosomal membrane traffic and macroautophagy in various cell types; however, its role in Sertoli cells remains unclear. Here, we generated a mouse line in which Pik3c3 was specifically deleted in Sertoli cells (cKO) and found that after one round of normal spermatogenesis, the cKO mice quickly became infertile and showed disruption of Sertoli cell polarity, loss of germ cells and impaired spermiogenesis. Subsequent proteomics and phosphoproteomics analyses enriched the F-actin cytoskeleton network involved in the disorganized Sertoli-cell structure in cKO testis, and showed significantly increased expression of the F-actin negative regulator SCIN and reduced phosphorylation of the α-tubulin deacetylase HDAC6. Our results further demonstrated that the accumulation of SCIN in cKO Sertoli cells caused the disassembly of the F-actin cytoskeleton, which was related to the failure of SCIN degradation through the autophagy-lysosome pathway. Additionally, we found that the phosphorylation of HDAC6 at site S59 by PIK3C3 was essential for its degradation through the ubiquitin-proteasome pathway. As a result, the HDAC6 that accumulated in cKO Sertoli cells deacetylated SCIN at site K189 and led to a disorganized F-actin cytoskeleton. Taken together, our findings elucidate the indispensable role of PIK3C3 in maintaining Sertoli cell polarity and reveal a new mechanism in which both its protein kinase activity and its regulation of autophagy are required for the stabilization of the actin cytoskeleton.
HostingRepository	PRIDE
AnnounceDate	2024-08-09
AnnouncementXML	Submission_2024-08-09_05:03:25.480.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	克瀚 王
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	acetylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2022-08-23 05:27:27	ID requested
⏵ 1	2024-08-09 05:03:26	announced
2	2024-10-22 06:53:44	announced	2024-10-22: Updated project metadata.

10.1080/15548627.2023.2235195;

Wang K, Kong F, Qiu Y, Chen T, Fu J, Jin X, Su Y, Gu Y, Hu Z, Li J, Autophagy regulation and protein kinase activity of PIK3C3 controls sertoli cell polarity through its negative regulation on SCIN (scinderin). Autophagy, 19(11):2934-2957(2023) [pubmed]

submitter keyword: Sertoli cell, cell polarity, autophagy, F-actin, spermatogenesis, PIK3C3/VPS34

Jing Li
contact affiliation	State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu,China.
contact email	ljwth@njmu.edu.cn
lab head
克瀚 王
contact affiliation	Nanjing Medical University
contact email	wkhwkh01@163.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD036242
     1. Label: PRIDE project
     2. Name: PIK3C3/VPS34 controls Sertoli cell polarity in the mouse testis through the stabilization of the actin cytoskeleton