Glycobiology Advance Access originally published online on May 19, 2008
Glycobiology 2008 18(8):615-625; 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
Department of Cell Chemistry, Heidelberg Institute of Plant Sciences, University of Heidelberg, Im Neuenheimer Feld 360, 69120 Heidelberg, Germany
1 To whom correspondence should be addressed: Tel: +49-(0)6221-546286; Fax: +49-(0)6221-545859; e-mail: sstrahl{at}HIP.uni-heidelberg.de
Received on April 8, 2008; revised on May 9, 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 a heteromeric complex to initiate O-mannosylation in 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, including humans, suggesting a crucial function that is distinct from sPOMT2.
Key words: glycosylation / mannosylation / mannosyltransferase / POMT2 / POMT1
2 Present address: Department of Molecular Physiology and Biophysics, Howard Hughes Medical Institute, University of Iowa, Iowa City, IA 52240, USA.