Regulation of axonal HCN1 trafficking in perforant path involves expression of specific TRIP8b isoforms.

PloS One
Wiebke WilkarsRoland A Bender

Abstract

The functions of HCN channels in neurons depend critically on their subcellular localization, requiring fine-tuned machinery that regulates subcellular channel trafficking. Here we provide evidence that regulatory mechanisms governing axonal HCN channel trafficking involve association of the channels with specific isoforms of the auxiliary subunit TRIP8b. In the medial perforant path, which normally contains HCN1 channels in axon terminals in immature but not in adult rodents, we found axonal HCN1 significantly increased in adult mice lacking TRIP8b (TRIP8b(-/-)). Interestingly, adult mice harboring a mutation that results in expression of only the two most abundant TRIP8b isoforms (TRIP8b[1b/2](-/-)) exhibited an HCN1 expression pattern similar to wildtype mice, suggesting that presence of one or both of these isoforms (TRIP8b(1a), TRIP8b(1a-4)) prevents HCN1 from being transported to medial perforant path axons in adult mice. Concordantly, expression analyses demonstrated a strong increase of expression of both TRIP8b isoforms in rat entorhinal cortex with age. However, when overexpressed in cultured entorhinal neurons of rats, TRIP8b(1a), but not TRIP8b(1a-4), altered substantially the subcellular distribution of HCN1 by pro...Continue Reading

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Citations

Jan 11, 2014·PloS One·Yuan PanSheila A Baker
Apr 24, 2014·The Journal of Physiology·Mala M Shah
Oct 16, 2015·Neurobiology of Disease·Robert J HeuermannDane M Chetkovich
Nov 5, 2013·Progress in Neurobiology·Chao HeZhian Hu
Dec 12, 2012·Epilepsy & Behavior : E&B·Yoav NoamGregory L Holmes
Dec 27, 2018·Genes, Brain, and Behavior·Anne GüntherArnd Baumann
Aug 24, 2013·Journal of Neurophysiology·Darrin H BragerDaniel Johnston
Jan 24, 2014·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Wiebke WilkarsRoland A Bender

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Methods Mentioned

BETA
Knockout
genotyping
PCR
light microscopy
electron microscopy
transfection
protein assay

Software Mentioned

Image J
NIH Image J

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