Smad2 isoforms are differentially expressed during mouse brain development and aging.
Smad2 and Smad3 are central molecules of the TGFbeta and activin receptor complex mediated intracellular signaling pathway. They function as important transcription factors playing essential roles in brain development. Interestingly they are also known to be involved in the pathogenesis of various neurological disorders (including Alzheimer's disease). Due to structural differences in the N-terminal Mad homology domain 1, Smad2 and Smad3 differ in their ability to bind DNA directly. A splice form of Smad2 lacking exon3, Smad2(Deltaexon3), assumes features of Smad3, in that it can directly bind to DNA resulting in a functional hybrid of Smad2 and Smad3 properties. There is very little information available on the expression of Smad2 isoforms in the brain. We report here that Smad2(Deltaexon3) is the most abundant of the two Smad2 isoforms in mouse brain and that Smad expression pattern alters during development and aging. Neuronal expression of Smad2(Deltaexon3) was confirmed by a single-cell PCR approach. Moreover, Smad2(Deltaexon3) predominates in the nuclear fraction of neurons, suggesting special function during brain differentiation. Our data indicate that there may be a specific role for Smad2(Deltaexon3) in neurons.
Department for Molecular and Cellular Mechanisms of Neurodegeneration, University of Leipzig, Paul Flechsig Institute of Brain Research, Leipzig 04109, Germany. Uwe.Ueberham@medizin.uni-leipzig.de
Uwe
U
Ueberham
Peggy
P
Lange
Elke
E
Ueberham
Martina K
MK
Brückner
Maike
M
Hartlage-Rübsamen
Thomas
T
Pannicke
Susanne
S
Rohn
Michael
M
Cross
Thomas
T
Arendt
D000375:Aging / Q000235:genetics*; D017398:Alternative Splicing; D000818:Animals; D001921:Brain / Q000254:growth & development / Q000502:physiology*; D002478:Cells, Cultured; D015870:Gene Expression; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000502:physiology*; D020033:Protein Isoforms; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051899:Smad2 Protein / Q000235:genetics*; D013347:Subcellular Fractions / Q000502:physiology
D020033:Protein Isoforms; D051899:Smad2 Protein; C497783:Smad2 protein, mouse