In:
European Journal of Neuroscience, Wiley, Vol. 44, No. 7 ( 2016-10), p. 2483-2492
Abstract:
KALRN ( KAL ) is a Rho GEF that is highly involved in regulation of the actin cytoskeleton within dendrites. There are several isoforms of the protein that arise from differential splicing of KALRN 's 66 exons. KAL isoforms have different functions in development. For example, overexpression of the KAL 9 and KAL 12 isoforms induce dendritic elongation in early development. However, in mature neurons KAL 9 overexpression reduces dendritic length, a phenotype also observed in normal human ageing. We therefore hypothesized that KAL 9 would have increased expression with age, and undertook to evaluate the expression of individual KALRN exons throughout the adult lifespan. Postmortem human brain grey matter from Brodmann's area ( BA ) 11 and BA 47 derived from a cohort of 209 individuals without psychiatric or neurodegenerative disease, ranging in age from 16 to 91 years, were analysed for KALRN expression by Affymetrix exon array. Analysis of the exon array data in an isoform‐specific manner, as well as confirmatory isoform‐specific qPCR studies, indicated that the longer KAL 9 and KAL 12 isoforms demonstrated a statistically significant, but modest, increase with age. The small magnitude of the age effect suggests that inter‐individual factors other than age likely contribute to a higher degree to KAL 9 and KAL 12 expression. In contrast to KAL 9 and KAL 12, global KALRN expression did not increase with age. Our work suggests that global measures of KALRN gene expression may be misleading and future studies should focus on isoform‐specific quantification.
Type of Medium:
Online Resource
ISSN:
0953-816X
,
1460-9568
DOI:
10.1111/ejn.2016.44.issue-7
Language:
English
Publisher:
Wiley
Publication Date:
2016
detail.hit.zdb_id:
2005178-5
SSG:
12
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