Autophagy regulates spermatid differentiation via degradation of PDLIM1

Autophagy. 2016 Sep;12(9):1575-92. doi: 10.1080/15548627.2016.1192750. Epub 2016 Jun 16.

Abstract

Spermiogenesis is a complex and highly ordered spermatid differentiation process that requires reorganization of cellular structures. We have previously found that Atg7 is required for acrosome biogenesis. Here, we show that autophagy regulates the round and elongating spermatids. Specifically, we found that Atg7 is required for spermatozoa flagella biogenesis and cytoplasm removal during spermiogenesis. Spermatozoa motility of atg7-null mice dropped significantly with some extra-cytoplasm retained on the mature sperm head. These defects are associated with an impairment of the cytoskeleton organization. Functional screening revealed that the negative cytoskeleton organization regulator, PDLIM1 (PDZ and LIM domain 1 [elfin]), needs to be degraded by the autophagy-lysosome-dependent pathway to facilitate the proper organization of the cytoskeleton. Our results thus provide a novel mechanism showing that autophagy regulates cytoskeleton organization mainly via degradation of PDLIM1 to facilitate the differentiation of spermatids.

Keywords: Atg7; PDLIM1; autophagy; cytoskeleton organization; spermatid differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagy*
  • Autophagy-Related Protein 7 / genetics
  • Cell Differentiation
  • Computational Biology
  • Cycloheximide / chemistry
  • Cytoplasm / metabolism
  • Cytoskeleton / metabolism
  • Fibroblasts / metabolism
  • Flagella / metabolism
  • Gene Expression Regulation*
  • LIM Domain Proteins / genetics*
  • LIM Domain Proteins / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microtubules / metabolism
  • Spermatids / cytology*
  • Spermatogenesis
  • Spermatozoa / cytology
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism*

Substances

  • Atg7 protein, mouse
  • LIM Domain Proteins
  • Ldb2 protein, mouse
  • Transcription Factors
  • Cycloheximide
  • Autophagy-Related Protein 7