title: Age-dependent increase in Kalirin-9 and Kalirin-12 transcripts in human orbitofrontal cortex.
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.
authors.affiliation: Department of Psychiatry, University of Pittsburgh Medical School, Pittsburgh, PA, USA.
authors.forename: Melanie J
authors.initials: MJ
authors.lastname: Grubisha
authors.affiliation: Department of Biostatistics, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Chien-Wei
authors.initials: CW
authors.lastname: Lin
authors.affiliation: Department of Biostatistics, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: George C
authors.initials: GC
authors.lastname: Tseng
authors.affiliation: Departments of Physiology and Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Penzes
authors.affiliation: Department of Psychiatry, University of Pittsburgh Medical School, Pittsburgh, PA, USA.|Center for Neuroscience, University of Pittsburgh, Pittsburgh, PA, USA.|Departments of Psychiatry, Pharmacology and Toxicology, Campbell Family Mental Health Research Institute of CAMH, University of Toronto, Toronto, ON, Canada.
authors.forename: Etienne
authors.initials: E
authors.lastname: Sibille
authors.affiliation: Departments of Psychiatry and Neurology, University of Pittsburgh School of Medicine, Biomedical Science Tower, Rm W-1645, 3811 O'Hara Street, Pittsburgh, PA, 15213-2593, USA. sweetra@upmc.edu.|Mental Illness Research, Education, and Clinical Center, VA Pittsburgh Healthcare System, Pittsburgh, PA, USA. sweetra@upmc.edu.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Sweet
mesh_terms: D000328:Adult; D000375:Aging / Q000502:physiology*; D002478:Cells, Cultured; D005260:Female; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000378:metabolism*; D010641:Phenotype; D017397:Prefrontal Cortex / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D020662:Guanine Nucleotide Exchange Factors; C503866:KALRN protein, human; D017346:Protein Serine-Threonine Kinases
keywords: Kalirin; dendritic complexity; human ageing; postmortem