Glycobiology Advance Access published online on May 19, 2008
Glycobiology, doi:10.1093/glycob/cwn042
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POMT2, a key enzyme in Walker-Warburg-Syndrome: somatic sPOMT2 but not testis specific tPOMT2 is crucial for mannosyltransferase activity in vivo
Heidelberg Institute of Plant Sciences, Dept. V Cell Chemistry, University of Heidelberg, Im Neuenheimer Feld 360, 69120 Heidelberg, Germany
Address correspondence to: Prof. Dr. Sabine Strahl, Heidelberg Institute of Plant Sciences, Dept. V Cell Chemistry, University of Heidelberg, Im Neuenheimer Feld 360, 69120 Heidelberg, Germany, Phone: +49 (0)6221 546286, Fax: +49 (0)6221 545859, E-mail: sstrahl{at}HIP.uni-heidelberg.de
Received on April 8, 2008; accepted on May 12, 2008
O-mannosylation represents an evolutionarily conserved, essential protein modification. In mammals the protein O-mannosyltransferases POMT1 and POMT2 act as heteromeric complex to initiate O-mannosylation at the endoplasmic reticulum. Mutations in human POMT1 and POMT2 cause a group of congenital muscular dystrophies due to reduced O-glycosylation of 
-dystroglycan. The most severe of these autosomal recessive conditions is Walker-Warburg-Syndrome (WWS) with severe brain and ocular involvement. We previously showed in the murine model that Pomt1 is expressed in WWS-related tissues both during embryogenesis and in adults. Whereas there is only a single Pomt1 transcript in adult mice, we demonstrated that there are two Pomt2 transcripts, somatic sPomt2 and testis specific tPomt2.
In this study we demonstrate that sPomt2, but not tPomt2, is prominently expressed in mouse embryos, in the tissues that are most severely affected in WWS (developing muscle, eye and brain). Correlation of POMT transcripts and protein isoforms with POMT mannosyltransferase enzyme activity demonstrates that sPOMT2-POMT1 complexes catalyze mannosyltransfer in adult somatic tissues and testis. It is suggested that the gonadal defects described in some WWS cases are associated with defects in O-mannosylation. Our data further show that whereas sPOMT2 is widely expressed, tPOMT2 is restricted to the acrosome of male germ cells and is not involved in the biosynthesis of O-mannosyl glycans in vivo. We prove that tPOMT2 is highly conserved among mammals and humans suggesting a crucial function that is distinct from sPOMT2.
Key words: glycosylation / mannosylation / mannosyltransferase / POMT2 / POMT1
1 Present address: Howard Hughes Medical Institute, Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, IA 52240, United States of America
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