title: TRIP8b is required for maximal expression of HCN1 in the mouse retina.
abstract: Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are cation-selective channels present in retina, brain and heart. The activity of HCN channels contributes to signal integration, cell excitability and pacemaker activity. HCN1 channels expressed in photoreceptors participate in keeping light responses transient and are required for normal mesopic vision. The subcellular localization of HCN1 varies among cell types. In photoreceptors HCN1 is concentrated in the inner segments while in other retinal neurons, HCN1 is evenly distributed though the cell. This is in contrast to hippocampal neurons where HCN1 is concentrated in a subset of dendrites. A key regulator of HCN1 trafficking and activity is tetratricopeptide repeat-containing Rab8b interacting protein (TRIP8b). Multiple splice isoforms of TRIP8b are expressed throughout the brain and can differentially regulate the surface expression and activity of HCN1. The purpose of the present study was to determine which isoforms of TRIP8b are expressed in the retina and to test if loss of TRIP8b alters HCN1 expression or trafficking. We found that TRIP8b colocalizes with HCN1 in multiple retina neurons and all major splice isoforms of TRIP8b are expressed in the retina. Photoreceptors express three different isoforms. In TRIP8b knockout mice, the ability of HCN1 to traffic to the surface of retinal neurons is unaffected. However, there is a large decrease in the total amount of HCN1. We conclude that TRIP8b in the retina is needed to achieve maximal expression of HCN1.
authors.affiliation: Department of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Department of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America.
authors.forename: Sajag
authors.initials: S
authors.lastname: Bhattarai
authors.affiliation: Department of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America.
authors.forename: Modestos
authors.initials: M
authors.lastname: Modestou
authors.affiliation: Department of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America.
authors.forename: Arlene V
authors.initials: AV
authors.lastname: Drack
authors.affiliation: The Ken & Ruth Davee Department of Neurology and Clinical Neurosciences and Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America.
authors.forename: Dane M
authors.initials: DM
authors.lastname: Chetkovich
authors.affiliation: Department of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America ; Department of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America.
authors.forename: Sheila A
authors.initials: SA
authors.lastname: Baker
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D005425:Flicker Fusion; D005786:Gene Expression Regulation; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels / Q000235:genetics* / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D000074401:Peroxins; D010786:Photoreceptor Cells / Q000378:metabolism; D011485:Protein Binding; D020033:Protein Isoforms; D021381:Protein Transport; D012160:Retina / Q000378:metabolism*
chemical_list: D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D008565:Membrane Proteins; D000074401:Peroxins; C501732:Pex5l protein, mouse; D020033:Protein Isoforms