New aspects of tropomyosin-regulated neuritogenesis revealed by the deletion of Tm5NM1 and 2.
Previous studies have shown that the overexpression of tropomyosins leads to isoform-specific alterations in the morphology of subcellular compartments in neuronal cells. Here we have examined the role of the most abundant set of isoforms from the gamma-Tm gene by knocking out the alternatively spliced C-terminal exon 9d. Despite the widespread location of exon 9d-containing isoforms, mice were healthy and viable. Compensation by products containing the C-terminal exon 9c was seen in the adult brain. While neurons from these mice show a mild phenotype at one day in culture, neurons revealed a significant morphological alteration with an increase in the branching of dendrites and axons after four days in culture. Our data suggest that this effect is mediated via altered stability of actin filaments in the growth cones. We conclude that exon 9d-containing isoforms are not essential for survival of neuronal cells and that isoform choice from the gamma-Tm gene is flexible in the brain. Although functional redundancy does not exist between tropomyosin genes, these results suggest that significant redundancy exists between products from the same gene.
Fath
Thomas
T
Department of Anatomy, School of Medical Sciences, University of New South Wales, NSW, Australia. t.fath@unsw.edu.au
Agnes Chan
Yee-Ka
YK
Vrhovski
Bernadette
B
Clarke
Hamish
H
Curthoys
Nikki
N
Hook
Jeff
J
Lemckert
Frances
F
Schevzov
Galina
G
Tam
Patrick
P
Watson
Catherine M
CM
Khoo
Poh-Lynn
PL
Gunning
Peter
P
D017398:Alternative Splicing / Q000235:genetics / Q000502:physiology; D000818:Animals; D001369:Axons / Q000378:metabolism; D001921:Brain / Q000166:cytology / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D004591:Electrophoresis, Polyacrylamide Gel; D007150:Immunohistochemistry; D051379:Mice; D055495:Neurogenesis / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D010641:Phenotype; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D014335:Tropomyosin / Q000235:genetics / Q000378:metabolism*
D020033:Protein Isoforms; C411923:Tpm3 protein, mouse; D014335:Tropomyosin