Amyotrophic lateral sclerosis-associated mutant profilin 1 increases dendritic arborisation and spine formation in primary hippocampal neurons.
Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease and familial ALS accounts for 10% of cases. The identification of familial ALS mutations in the actin-binding protein profilin 1 directly implicates actin dynamics and regulation in the pathogenesis of ALS. The mechanism by which these mutations cause ALS is unknown. In this study we show that expression of the ALS-associated actin-binding deficient mutant of PFN1 (PFN1(C71G)) results in increased dendritic arborisation and spine formation, and cytoplasmic inclusions in cultured mouse hippocampal neurons.
Neurodegeneration and Repair Unit, School of Medical Sciences, University of New South Wales, Australia.
Merryn
M
Brettle
Neurodegeneration and Repair Unit, School of Medical Sciences, University of New South Wales, Australia.
Alexandra K
AK
Suchowerska
Dementia Research Unit, School of Medical Sciences, University of New South Wales, Australia.
Sook W
SW
Chua
Dementia Research Unit, School of Medical Sciences, University of New South Wales, Australia. Electronic address: l.ittner@unsw.edu.au.
Lars M
LM
Ittner
Neurodegeneration and Repair Unit, School of Medical Sciences, University of New South Wales, Australia. Electronic address: t.fath@unsw.edu.au.
Thomas
T
Fath
D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D000818:Animals; D003712:Dendrites / Q000378:metabolism / Q000648:ultrastructure*; D049229:Dendritic Spines / Q000378:metabolism / Q000648:ultrastructure; D057809:HEK293 Cells; D006624:Hippocampus / Q000166:cytology*; D006801:Humans; D008810:Mice, Inbred C57BL; D009154:Mutation; D009474:Neurons / Q000378:metabolism / Q000648:ultrastructure; D061251:Primary Cell Culture; D051304:Profilins / Q000235:genetics / Q000378:metabolism*; D066329:Protein Aggregates
C495738:PFN1 protein, human; D051304:Profilins; D066329:Protein Aggregates
Actin cytoskeleton; Amyotrophic lateral sclerosis; Profilin 1