Defects in secretory pathway trafficking during sperm development in Adam2 knockout mice.
Adam2-null and Adam3-null male mice exhibit reduced levels of one or more ADAM proteins on mature sperm, in addition to the loss of the genetically targeted protein. ADAM protein loss was believed to occur posttranslationally, although the timing of loss and the mechanism by which the loss occurred were not explored. In this study we have found that in Adam3-null mice, fertilin beta (also known as ADAM2) is lost during the formation of testicular sperm. In Adam2-null males, most cyritestin (ADAM3) protein is also lost at this stage, but 25% of cyritestin is lost later, during sperm passage through the epididymis. Although normal levels of cyritestin are synthesized and acquire Endoglycosidase H resistance, indicating transit through the Golgi, the protein does not reach the cell surface. We also discovered that the majority of both fertilin beta and cyritestin are found in a Triton X-100 insoluble compartment on testicular sperm, when most of the cyritestin was observed on the cell surface. This insoluble compartment may represent a sorting platform, because in Adam2-knockout cells, only a small fraction of the cyritestin becomes Triton X-100 insoluble. Thus, it appears that cyritestin loss in Adam2-knockout mice may result, at least in part, from a disruption in protein trafficking.
Stein
Kathryn K
KK
Section of Molecular and Cellular Biology, University of California, Davis, 95616, USA.
Go
Jowell C
JC
Primakoff
Paul
P
Myles
Diana G
DG
D051722:ADAM Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D029681:Arabidopsis Proteins; D002462:Cell Membrane / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004822:Epididymis / Q000166:cytology / Q000378:metabolism; D000072196:Fertilins; D008297:Male; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008970:Molecular Weight; D046912:Multiprotein Complexes; D017830:Octoxynol / Q000737:chemistry; D011499:Protein Processing, Post-Translational; D021381:Protein Transport / Q000235:genetics; D013094:Spermatozoa / Q000378:metabolism*; D013737:Testis / Q000166:cytology / Q000378:metabolism; D015534:Trans-Activators
D029681:Arabidopsis Proteins; C491466:MBF1 protein, Arabidopsis; D008562:Membrane Glycoproteins; D046912:Multiprotein Complexes; D015534:Trans-Activators; D017830:Octoxynol; D051722:ADAM Proteins; C000606458:Adam2 protein, mouse; C485429:Adam3 protein, mouse; D000072196:Fertilins