FYCO1 and autophagy control the integrity of the haploid male germ cell-specific RNP granules

Autophagy. 2017 Feb;13(2):302-321. doi: 10.1080/15548627.2016.1261319. Epub 2016 Dec 8.

Abstract

Ribonucleoprotein (RNP) granules play a major role in compartmentalizing cytoplasmic RNA regulation. Haploid round spermatids that have exceptionally diverse transcriptomes are characterized by a unique germ cell-specific RNP granule, the chromatoid body (CB). The CB shares many characteristics with somatic RNP granules but also has germline-specific features. The CB appears to be a central structure in PIWI-interacting RNA (piRNA)-targeted RNA regulation. Here, we identified a novel CB component, FYCO1, which is involved in the intracellular transport of autophagic vesicles in somatic cells. We demonstrated that the CB is associated with autophagic activity. Induction of autophagy leads to the recruitment of lysosomal vesicles onto the CB in a FYCO1-dependent manner as demonstrated by the analysis of a germ cell-specific Fyco1 conditional knockout mouse model. Furthermore, in the absence of FYCO1, the integrity of the CB was affected and the CB was fragmented. Our results suggest that RNP granule homeostasis is regulated by FYCO1-mediated autophagy.

Keywords: FYCO1; RNP granule; autophagy; chromatoid body; germ cell; knockout; lysosome; posttranscriptional; spermatogenesis; vesicle.

MeSH terms

  • Animals
  • Argonaute Proteins / genetics
  • Argonaute Proteins / metabolism
  • Autophagosomes / metabolism
  • Autophagosomes / ultrastructure
  • Autophagy*
  • Cytoplasmic Granules / metabolism*
  • Cytoplasmic Granules / ultrastructure
  • Cytoskeletal Proteins
  • DNA-Binding Proteins / metabolism*
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Gene Ontology
  • Haploidy*
  • Lysosomes / metabolism
  • Lysosomes / ultrastructure
  • Male
  • Mice, Knockout
  • Microtubules / metabolism
  • Microtubules / ultrastructure
  • Nerve Tissue Proteins / metabolism*
  • Organ Specificity
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoinositide-3 Kinase Inhibitors
  • Protein Binding
  • Protein Transport
  • Ribonucleoproteins / metabolism*
  • Spermatids / metabolism
  • Spermatids / ultrastructure
  • Spermatogenesis
  • Spermatozoa / cytology*
  • Spermatozoa / metabolism*
  • Spermatozoa / ultrastructure
  • Testis / metabolism

Substances

  • Argonaute Proteins
  • Cytoskeletal Proteins
  • DNA-Binding Proteins
  • Nerve Tissue Proteins
  • Phosphatidylinositol 3-Kinases
  • Phosphoinositide-3 Kinase Inhibitors
  • Ribonucleoproteins
  • Piwil2 protein, mouse
  • Rufy3 protein, mouse