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

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Regulation of axonal HCN1 trafficking in perforant path involves expression of specific TRIP8b isoforms. / Wilkars, Wiebke; Liu, Zhiqiang; Lewis, Alan S; Stoub, Travis R; Ramos, Elena M; Brandt, Nicola; Nicholson, Daniel A; Chetkovich, Dane M; Bender, Roland.

In: PLOS ONE, Vol. 7, No. 2, 2, 2012, p. 32181.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Wilkars, W, Liu, Z, Lewis, AS, Stoub, TR, Ramos, EM, Brandt, N, Nicholson, DA, Chetkovich, DM & Bender, R 2012, 'Regulation of axonal HCN1 trafficking in perforant path involves expression of specific TRIP8b isoforms.', PLOS ONE, vol. 7, no. 2, 2, pp. 32181. https://doi.org/10.1371/journal.pone.0032181

APA

Wilkars, W., Liu, Z., Lewis, A. S., Stoub, T. R., Ramos, E. M., Brandt, N., Nicholson, D. A., Chetkovich, D. M., & Bender, R. (2012). Regulation of axonal HCN1 trafficking in perforant path involves expression of specific TRIP8b isoforms. PLOS ONE, 7(2), 32181. [2]. https://doi.org/10.1371/journal.pone.0032181

Vancouver

Wilkars W, Liu Z, Lewis AS, Stoub TR, Ramos EM, Brandt N et al. Regulation of axonal HCN1 trafficking in perforant path involves expression of specific TRIP8b isoforms. PLOS ONE. 2012;7(2):32181. 2. https://doi.org/10.1371/journal.pone.0032181

Bibtex

@article{3aea63c6bd8e4cdea98b8995db8f4cc8,
title = "Regulation of axonal HCN1 trafficking in perforant path involves expression of specific TRIP8b isoforms.",
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 promoting somatodendritic and reducing axonal expression of the channels. Taken together, we conclude that TRIP8b isoforms are important regulators of HCN1 trafficking in entorhinal neurons and that the alternatively-spliced isoform TRIP8b(1a) could be responsible for the age-dependent redistribution of HCN channels out of perforant path axon terminals.",
keywords = "Animals, Female, Cells, Cultured, Mice, Mice, Inbred C57BL, Protein Transport, Rats, Rats, Wistar, Transfection, Axons/*metabolism, Green Fluorescent Proteins/metabolism, Subcellular Fractions/metabolism, Cyclic Nucleotide-Gated Cation Channels/*metabolism, Dentate Gyrus/cytology/metabolism/ultrastructure, Entorhinal Cortex/cytology/metabolism, Membrane Proteins/deficiency/*metabolism, Perforant Pathway/cytology/*metabolism, Potassium Channels/*metabolism, Protein Isoforms/metabolism, Tissue Embedding, Animals, Female, Cells, Cultured, Mice, Mice, Inbred C57BL, Protein Transport, Rats, Rats, Wistar, Transfection, Axons/*metabolism, Green Fluorescent Proteins/metabolism, Subcellular Fractions/metabolism, Cyclic Nucleotide-Gated Cation Channels/*metabolism, Dentate Gyrus/cytology/metabolism/ultrastructure, Entorhinal Cortex/cytology/metabolism, Membrane Proteins/deficiency/*metabolism, Perforant Pathway/cytology/*metabolism, Potassium Channels/*metabolism, Protein Isoforms/metabolism, Tissue Embedding",
author = "Wiebke Wilkars and Zhiqiang Liu and Lewis, {Alan S} and Stoub, {Travis R} and Ramos, {Elena M} and Nicola Brandt and Nicholson, {Daniel A} and Chetkovich, {Dane M} and Roland Bender",
year = "2012",
doi = "10.1371/journal.pone.0032181",
language = "English",
volume = "7",
pages = "32181",
journal = "PLOS ONE",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "2",

}

RIS

TY - JOUR

T1 - Regulation of axonal HCN1 trafficking in perforant path involves expression of specific TRIP8b isoforms.

AU - Wilkars, Wiebke

AU - Liu, Zhiqiang

AU - Lewis, Alan S

AU - Stoub, Travis R

AU - Ramos, Elena M

AU - Brandt, Nicola

AU - Nicholson, Daniel A

AU - Chetkovich, Dane M

AU - Bender, Roland

PY - 2012

Y1 - 2012

N2 - 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 promoting somatodendritic and reducing axonal expression of the channels. Taken together, we conclude that TRIP8b isoforms are important regulators of HCN1 trafficking in entorhinal neurons and that the alternatively-spliced isoform TRIP8b(1a) could be responsible for the age-dependent redistribution of HCN channels out of perforant path axon terminals.

AB - 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 promoting somatodendritic and reducing axonal expression of the channels. Taken together, we conclude that TRIP8b isoforms are important regulators of HCN1 trafficking in entorhinal neurons and that the alternatively-spliced isoform TRIP8b(1a) could be responsible for the age-dependent redistribution of HCN channels out of perforant path axon terminals.

KW - Animals

KW - Female

KW - Cells, Cultured

KW - Mice

KW - Mice, Inbred C57BL

KW - Protein Transport

KW - Rats

KW - Rats, Wistar

KW - Transfection

KW - Axons/metabolism

KW - Green Fluorescent Proteins/metabolism

KW - Subcellular Fractions/metabolism

KW - Cyclic Nucleotide-Gated Cation Channels/metabolism

KW - Dentate Gyrus/cytology/metabolism/ultrastructure

KW - Entorhinal Cortex/cytology/metabolism

KW - Membrane Proteins/deficiency/metabolism

KW - Perforant Pathway/cytology/metabolism

KW - Potassium Channels/metabolism

KW - Protein Isoforms/metabolism

KW - Tissue Embedding

KW - Animals

KW - Female

KW - Cells, Cultured

KW - Mice

KW - Mice, Inbred C57BL

KW - Protein Transport

KW - Rats

KW - Rats, Wistar

KW - Transfection

KW - Axons/metabolism

KW - Green Fluorescent Proteins/metabolism

KW - Subcellular Fractions/metabolism

KW - Cyclic Nucleotide-Gated Cation Channels/metabolism

KW - Dentate Gyrus/cytology/metabolism/ultrastructure

KW - Entorhinal Cortex/cytology/metabolism

KW - Membrane Proteins/deficiency/metabolism

KW - Perforant Pathway/cytology/metabolism

KW - Potassium Channels/metabolism

KW - Protein Isoforms/metabolism

KW - Tissue Embedding

U2 - 10.1371/journal.pone.0032181

DO - 10.1371/journal.pone.0032181

M3 - SCORING: Journal article

VL - 7

SP - 32181

JO - PLOS ONE

JF - PLOS ONE

SN - 1932-6203

IS - 2

M1 - 2

ER -