PMID- 37119967
OWN - NLM
STAT- MEDLINE
DCOM- 20230605
LR  - 20230606
IS  - 1872-8057 (Electronic)
IS  - 0303-7207 (Linking)
VI  - 571
DP  - 2023 Jul 1
TI  - Regulation of Sertoli cell function by planar cell polarity (PCP) protein Fjx1.
PG  - 111936
LID - S0303-7207(23)00087-4 [pii]
LID - 10.1016/j.mce.2023.111936 [doi]
AB  - Four-jointed box kinase 1 (Fjx1) is a planar cell polarity (PCP) protein and a 
      member of the Fat (FAT atypical cadherin 1)/Dchs (Dachsous cadherin-related 
      protein)/Fjx1 PCP complex. Fjx1 is also a non-receptor Ser/Thr protein kinase 
      capable of phosphorylating Fat1 at is extracellular cadherin domains when it is 
      being transported across the Golgi system. As such, Fjx1 is a Golgi-based 
      regulator of Fat1 function by determining its extracellular deposition. Herein, 
      Fjx1 was found to localize across the Sertoli cell cytoplasm, partially 
      co-localized with the microtubules (MTs) across the seminiferous epithelium. It 
      was most notable at the apical ES (ectoplasmic specialization) and basal ES, 
      displaying distinctive stage-specific expression. The apical ES and basal ES are 
      the corresponding testis-specific cell adhesion ultrastructures at the 
      Sertoli-elongated spermatid interface and the Sertoli cell-cell interface, 
      respectively, consistent with the role of Fjx1 as a Golgi-associated Ser/Thr 
      kinase that modulates the Fat (and/or Dchs) integral membrane proteins. Its 
      knockdown (KD) by RNAi using specific Fjx1 siRNA duplexes versus non-targeting 
      negative control siRNA duplexes was found to perturb the Sertoli cell tight 
      junction function, as well as perturbing the function and organization of MT and 
      actin. While Fjx1 KD did not affect the steady-state levels of almost two dozens 
      of BTB-associated Sertoli cell proteins, including structural and regulatory 
      proteins, its KD was found to down-regulate Fat1 (but not Fat2, 3, and 4) and to 
      up-regulate Dchs1 (but not Dchs2) expression. Based on results of biochemical 
      analysis, Fjx1 KD was found to be capable of abolishing phosphorylation of its 
      putative substrate Fat1 at its Ser/Thr sites, but not at its Tyr site, 
      illustrating an intimate functional relationship of Fjx1 and Fat1 in Sertoli 
      cells.
CI  - Copyright (c) 2023 Elsevier B.V. All rights reserved.
FAU - Bu, Tiao
AU  - Bu T
AD  - Institute of Reproductive Medicine, Medical School of Nantong University, 
      Nantong, Jiangsu, 226001, China.
FAU - Li, Xinyao
AU  - Li X
AD  - Institute of Reproductive Medicine, Medical School of Nantong University, 
      Nantong, Jiangsu, 226001, China.
FAU - Wang, Lingling
AU  - Wang L
AD  - Institute of Reproductive Medicine, Medical School of Nantong University, 
      Nantong, Jiangsu, 226001, China.
FAU - Wu, Xiaolong
AU  - Wu X
AD  - Department of Urology and Andrology, Sir Run Run Shaw Hospital, Zhejiang 
      University School of Medicine, Hangzhou, Zhejiang, 310016, China.
FAU - Gao, Sheng
AU  - Gao S
AD  - Institute of Reproductive Medicine, Medical School of Nantong University, 
      Nantong, Jiangsu, 226001, China.
FAU - Yun, Damin
AU  - Yun D
AD  - Institute of Reproductive Medicine, Medical School of Nantong University, 
      Nantong, Jiangsu, 226001, China.
FAU - Li, Linxi
AU  - Li L
AD  - The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical 
      University, Wenzhou, Zhejiang, 325027, China.
FAU - Sun, Fei
AU  - Sun F
AD  - Institute of Reproductive Medicine, Medical School of Nantong University, 
      Nantong, Jiangsu, 226001, China. Electronic address: sunfei@ntu.edu.cn.
FAU - Cheng, C Yan
AU  - Cheng CY
AD  - Institute of Reproductive Medicine, Medical School of Nantong University, 
      Nantong, Jiangsu, 226001, China. Electronic address: cyancheng@ntu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230427
PL  - Ireland
TA  - Mol Cell Endocrinol
JT  - Molecular and cellular endocrinology
JID - 7500844
RN  - 0 (Cadherins)
RN  - 0 (RNA, Small Interfering)
SB  - IM
MH  - Rats
MH  - Animals
MH  - Male
MH  - *Sertoli Cells/metabolism
MH  - *Spermatogenesis/genetics
MH  - Cell Polarity
MH  - Rats, Sprague-Dawley
MH  - Testis/metabolism
MH  - Seminiferous Epithelium/metabolism
MH  - Cadherins/metabolism
MH  - RNA, Small Interfering/metabolism
MH  - Blood-Testis Barrier/metabolism
OTO - NOTNLM
OT  - Blood-testis barrier
OT  - Fat/Dchs/Fjx1 PCP complex
OT  - Fertility
OT  - Four-jointed box kinase
OT  - Infertility
OT  - Planar cell polarity
OT  - Testis
COIS- Declaration of competing interest Nothing to declare of all authors.
EDAT- 2023/04/30 00:42
MHDA- 2023/06/05 06:42
CRDT- 2023/04/29 19:26
PHST- 2023/02/27 00:00 [received]
PHST- 2023/04/16 00:00 [revised]
PHST- 2023/04/19 00:00 [accepted]
PHST- 2023/06/05 06:42 [medline]
PHST- 2023/04/30 00:42 [pubmed]
PHST- 2023/04/29 19:26 [entrez]
AID - S0303-7207(23)00087-4 [pii]
AID - 10.1016/j.mce.2023.111936 [doi]
PST - ppublish
SO  - Mol Cell Endocrinol. 2023 Jul 1;571:111936. doi: 10.1016/j.mce.2023.111936. Epub 
      2023 Apr 27.