TMF/ARA160: A key regulator of sperm development.
TMF/ARA160 is a Golgi-associated protein to which several cellular activities have been attributed. These include, trafficking of Golgi-derived vesicles and E3 ubiquitin ligase activity. Here we show that TMF/ARA160 is required for the onset of key processes which underlie the development of mature sperm in mammals. TMF/ARA160 is highly expressed in specific spermatogenic stages. While the protein is not detected in the spermatogenic progenitor cells - spermatogonia, it accumulates in the Golgi of spermatocytes and spermatids but then disappears and is absent from spermatozoa and epididymal sperm cells. Mice that are homozygous null for TMF develop normally are healthy and the females are fertile. However, the males are sterile and their spermatids suffer from several developmental defects. They lack homing of Golgi-derived proacrosomal vesicles to the perinuclear surface, resulting in spermatozoa and epididymal sperm cells which lack acrosome. In a later developmental stage, the cytoplasm is not properly removed, thus resulting in spermatids which bare the nucleus with tightly packed DNA, surrounded by a cytoplasm. Finally, the spermatozoa of TMF(-/-) mice also suffer from misshapen heads, tails coiling around the sperm heads, and lack of motility. Taken together our findings portray TMF/ARA160 as a key regulator which is essential for the onset of key events in the differentiation and maturation of mammalian sperm and whose absence severely compromises their ability to fertilize ova.
Lerer-Goldshtein
Tal
T
The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.
Bel
Shai
S
Shpungin
Sally
S
Pery
Erez
E
Motro
Benny
B
Goldstein
Ronald S
RS
Bar-Sheshet
Sarit Itach
SI
Breitbart
Haim
H
Nir
Uri
U
D000177:Acrosome / Q000737:chemistry / Q000648:ultrastructure; D008841:Actin Cytoskeleton / Q000648:ultrastructure; D000818:Animals; D002454:Cell Differentiation; D003593:Cytoplasm / Q000378:metabolism; D004268:DNA-Binding Proteins; D005260:Female; D006056:Golgi Apparatus / Q000378:metabolism; D000077614:Golgi Matrix Proteins; D007248:Infertility, Male / Q000235:genetics / Q000503:physiopathology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D008928:Mitochondria / Q000648:ultrastructure; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013077:Sperm Head / Q000648:ultrastructure; D013079:Sperm Maturation / Q000502:physiology*; D013081:Sperm Motility; D013082:Sperm Tail / Q000648:ultrastructure; D013084:Sperm-Ovum Interactions / Q000502:physiology; D013087:Spermatids / Q000378:metabolism / Q000648:ultrastructure; D013090:Spermatocytes / Q000378:metabolism / Q000648:ultrastructure; D013094:Spermatozoa / Q000002:abnormalities / Q000502:physiology* / Q000648:ultrastructure; D014157:Transcription Factors; D044767:Ubiquitin-Protein Ligases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D033921:Vesicular Transport Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D004268:DNA-Binding Proteins; D000077614:Golgi Matrix Proteins; C554202:Tmf1 protein, mouse; D014157:Transcription Factors; D033921:Vesicular Transport Proteins; D044767:Ubiquitin-Protein Ligases