The DMWD protein from the myotonic dystrophy (DM1) gene region is developmentally regulated and is present most prominently in synapse-dense brain areas.
The DMWD gene is located in the myotonic dystrophy (DM1) gene cluster on 19q, just upstream of the DMPK gene. RNA and protein products of this gene are ubiquitously expressed in all adult tissues, but occur most abundant in testes and brain. Altered expression of DMWD mRNA in DM1 patients has been observed, suggesting a role of the DMWD gene products in disease manifestation. Here we focussed on DMWD expression in mouse brain and followed mRNA and protein levels and (intra)cellular location in developing brain in vivo as well as in differentiating neuronal cell cultures in vitro. In the interval between postnatal days P7 and P21, the steady-state level of DMWD mRNA remained constant, whereas the DMWD protein (doublet of 70 kDa) level gradually increased during the same period. The DMWD protein was expressed throughout the brain, at a low level in glial cells, more prominently in neurons and specifically in the neuropil of brain areas with a high density of synaptic connections. Intracellularly, DMWD was dispersed in a punctuate fashion throughout the neural cell body, the nucleus and the dendrites with their synapses, but was excluded from axons. Based on these findings and on new literature data concerning the role of DMWD homologs in lower eukaryotes, we discuss the possible role of DMWD in the brain-related symptoms seen in DM1 patients.
Westerlaken
Jolanda H A M
JH
Department of Cell Biology, NCMLS, UMC Radboud, University of Nijmegen, Geert Grooteplein Zuid 28, 6525 GA, Nijmegen, The Netherlands.
Van der Zee
Catharina E E M
CE
Peters
Wilma
W
Wieringa
Bé
B
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D001921:Brain / Q000166:cytology / Q000254:growth & development / Q000648:ultrastructure; D001923:Brain Chemistry / Q000502:physiology*; D002478:Cells, Cultured; D007150:Immunohistochemistry; D051379:Mice; D009223:Myotonic Dystrophy / Q000503:physiopathology; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure; D019581:Neuropil / Q000378:metabolism; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases / Q000032:analysis / Q000096:biosynthesis*; D011506:Proteins; D012333:RNA, Messenger / Q000032:analysis; D013569:Synapses / Q000378:metabolism
C081088:DMWD protein, human; C484123:Dm9 protein, mouse; D009687:Nuclear Proteins; D011506:Proteins; D012333:RNA, Messenger; D017346:Protein Serine-Threonine Kinases