Faculty Collaboration Database

Age-dependent increase in Kalirin-9 and Kalirin-12 transcripts in human orbitofrontal cortex. Eur J Neurosci 2016 Oct;44(7):2483-2492

Date

07/30/2016

Pubmed ID

27471199

Pubmed Central ID

PMC5048532

DOI

10.1111/ejn.13351

Scopus ID

2-s2.0-84982306466 (requires institutional sign-in at Scopus site)   6 Citations

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 KAL9 and KAL12 isoforms induce dendritic elongation in early development. However, in mature neurons KAL9 overexpression reduces dendritic length, a phenotype also observed in normal human ageing. We therefore hypothesized that KAL9 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 BA47 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 KAL9 and KAL12 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 KAL9 and KAL12 expression. In contrast to KAL9 and KAL12, 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.

Author List

Grubisha MJ, Lin CW, Tseng GC, Penzes P, Sibille E, Sweet RA

Author

Chien-Wei Lin PhD Associate Professor in the Institute for Health and Equity department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Aging
Cells, Cultured
Female
Guanine Nucleotide Exchange Factors
Humans
Male
Middle Aged
Neurogenesis
Neurons
Phenotype
Prefrontal Cortex