# MTMR7 regulates human spermatogonial stem cells proliferation and migration via targeting FLNB

## TL;DR

This study shows that MTMR7 regulates human spermatogonial stem cells by controlling FLNB and β-catenin signaling, offering new insights for treating male infertility.

## Contribution

The study is the first to demonstrate MTMR7's role in human SSCs via FLNB ubiquitination and β-catenin signaling.

## Key findings

- MTMR7 knockdown increases human SSC proliferation and migration, while overexpression inhibits these processes.
- MTMR7 interacts with FLNB and promotes its ubiquitination and degradation.
- MTMR7 regulates β-catenin signaling, which is essential for controlling human SSC behavior.

## Abstract

In the testes, spermatogonial stem cells (SSCs) maintain normal spermatogenesis through the dual potential of self-renewal and differentiation, which is essential for male fertility. Myotubularin-associated protein 7 (MTMR7), as a vital member of MTMR family with phosphatase activity, is involved in a variety of membrane transport processes through regulating the levels of phosphoinositides (PIPs). Our earlier research demonstrated that MTMR7 controls the cell cycle and maintains homeostasis in mouse SSCs by inhibiting PI3K/AKT signaling. However, its role in human SSCs has not been reported. This study found that knocking down MTMR7 increased the proliferation and migration of human SSCs, whereas MTMR7 overexpression inhibited these processes. Through mass spectrometry and immunoprecipitation, we identified filamin B (FLNB) as an interacting protein of MTMR7, and MTMR7 is required for FLNB ubiquitination and subsequent degradation. Further validation using immunofluorescence confirmed the involvement of the downstream β-catenin signaling. Altogether, this study is the first to demonstrate that MTMR7 regulates β-catenin expression and inhibits human SSCs proliferation and migration by mediating the ubiquitination and degradation of FLNB. These findings may offer new therapeutic strategies and target gene loci for treating male infertility caused by SSCs dysfunction.