TRIP8b Splice Forms Act in Concert to Regulate the Localization and Expression of HCN1 Channels in CA1 Pyramidal Neurons

Piskorowski, Rebecca A.; Santoro, Bina; Siegelbaum, Steven A.

doi:10.1016/j.neuron.2011.03.023

Cited by 70 publications

(116 citation statements)

References 30 publications

Supporting

Mentioning

108

Contrasting

Order By: Relevance

“…This correlation was observed both when comparing different hippocampi and when comparing different regions within a single hippocampus that differed in Cre-GFP expression, indicating that the effect of viral Dab1 knockdown was primarily cell autonomous. Dab1 knockdown also caused a reduction in distal enrichment of the HCN channel accessory subunit TRIP8b (Figure S5), which is important in the targeting of HCN1 to distal CA1 dendrites (Piskorowski et al, 2011; Lewis et al, 2009). Thus, disruption of Reelin signaling by viral knockdown of Dab1 or a loss-of-function Reelin mutation leads to a drastic impairment in the distal enrichment of HCN1 in the CA1 SLM region.…”

Section: Resultsmentioning

confidence: 99%

“…A second factor known to regulate HCN1 surface expression (Santoro et al, 2004, 2009) and dendritic targeting (Han et al, 2011; Piskorowski et al, 2011) is the brain-specific HCN channel auxiliary subunit TRIP8b. When the interaction between HCN1 and TRIP8b is prevented by deletion of the HCN1 conserved C-terminal tripeptide (Ser-Asn-Leu), the channels are no longer targeted to the distal dendrites and are uniformly expressed throughout the CA1 somatodendritic compartment (Piskorowski et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Reelin Signaling Specifies the Molecular Identity of the Pyramidal Neuron Distal Dendritic Compartment

Kupferman

Basu

Russo

et al. 2014

Cell

Self Cite

View full text Add to dashboard Cite

SUMMARY The apical dendrites of many neurons contain proximal and distal compartments that receive synaptic inputs from different brain regions. These compartments also contain distinct complements of ion channels that enable the differential processing of their respective synaptic inputs, making them functionally distinct. At present, the molecular mechanisms that specify dendritic compartments are not well understood. Here, we report that the extracellular matrix protein Reelin, acting through its downstream, intracellular Dab1 and Src family tyrosine kinase signaling cascade, is essential for establishing and maintaining the molecular identity of the distal dendritic compartment of cortical pyramidal neurons. We find that Reelin signaling is required for the striking enrichment of HCN1 and GIRK1 channels in the distal tuft dendrites of both hippocampal CA1 and neocortical layer 5 pyramidal neurons, where the channels actively filter inputs targeted to these dendritic domains.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Reelin Signaling Specifies the Molecular Identity of the Pyramidal Neuron Distal Dendritic Compartment

Kupferman

Basu

Russo

et al. 2014

Cell

Self Cite

View full text Add to dashboard Cite

show abstract

“…These isoforms control distinct aspects of HCN1 trafficking, such as promoting cell-surface expression or suppressing inappropriate trafficking to axons. Disruption of TRIP8b and HCN1 interactions leads to uniform distribution of HCN1 throughout the somatodendritic compartment (Piskorowski et al 2011). Thus, TRIP8b targets HCN1 to the appropriate dendrite location, although the details of how it accomplishes this remain to be worked out.…”

Section: Establishing the Membrane Excitability Of Dendritic Compartmmentioning

confidence: 99%

Development of Dendritic Form and Function

Lefebvre¹,

Sanes

Kay

2015

Annu. Rev. Cell Dev. Biol.

203

207

View full text Add to dashboard Cite

The nervous system is populated by numerous types of neurons, each bearing a dendritic arbor with a characteristic morphology. These type-specific features influence many aspects of a neuron's function, including the number and identity of presynaptic inputs and how inputs are integrated to determine firing properties. Here, we review the mechanisms that regulate the construction of cell type-specific dendrite patterns during development. We focus on four aspects of dendrite patterning that are particularly important in determining the function of the mature neuron: (a) dendrite shape, including branching pattern and geometry of the arbor; (b) dendritic arbor size;

show abstract

“…In 2004, Santoro and colleagues (11) identified an accessory subunit for HCN channels called TRIP8b (tetratricopetide repeat-containing Rab8b-interacting protein), which has recently been shown to target HCN1 and HCN2 channels to the membrane of the distal dendrites of CA1 pyramidal neurons (12,13). TRIP8b is a cytoplasmic protein primarily found in neurons that interacts with the carboxyl-terminal tripeptide of HCN channels (SNL in HCN1, -2, and -4; ANM in HCN3) and regulates their surface expression levels (11,14,15).…”

mentioning

confidence: 99%

Structure and stoichiometry of an accessory subunit TRIP8b interaction with hyperpolarization-activated cyclic nucleotide-gated channels

Bankston

Camp

DiMaio

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Ion channels operate in intact tissues as part of large macromolecular complexes that can include cytoskeletal proteins, scaffolding proteins, signaling molecules, and a litany of other molecules. The proteins that make up these complexes can influence the trafficking, localization, and biophysical properties of the channel. TRIP8b (tetratricopetide repeat-containing Rab8b-interacting protein) is a recently discovered accessory subunit of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels that contributes to the substantial dendritic localization of HCN channels in many types of neurons. TRIP8b interacts with the carboxyl-terminal region of HCN channels and regulates their cell-surface expression level and cyclic nucleotide dependence. Here we examine the molecular determinants of TRIP8b binding to HCN2 channels. Using a singlemolecule fluorescence bleaching method, we found that TRIP8b and HCN2 form an obligate 4:4 complex in intact channels. Fluorescence-detection size-exclusion chromatography and fluorescence anisotropy allowed us to confirm that two different domains in the carboxyl-terminal portion of TRIP8b-the tetratricopepide repeat region and the TRIP8b conserved region-interact with two different regions of the HCN carboxyl-terminal region: the carboxyl-terminal three amino acids (SNL) and the cyclic nucleotidebinding domain, respectively. And finally, using X-ray crystallography, we determined the atomic structure of the tetratricopepide region of TRIP8b in complex with a peptide of the carboxy-terminus of HCN2. Together, these experiments begin to uncover the mechanism for TRIP8b binding and regulation of HCN channels.ver the past two decades, it has become apparent that in living tissues ion channels do not function in isolation, but instead exist as macromolecular complexes that include auxiliary subunits, signaling molecules, scaffolding proteins, and cytoskeletal proteins (1-3). These accessory proteins associate with channels and alter their gating, expression levels, localization, and response to signals such as phosphorylation or internal calcium. Until recently, little was known about which proteins may associate with and modulate hyperpolarization-activated cyclic nucleotide-gated (HCN) channels under physiological conditions. HCN channels are members of the superfamily of voltage-gated channels that contain four subunits around a centrally located pore. Unlike most of the members of the family, however, HCN channels open in response to hyperpolarizing voltages (4, 5). In addition to their unique voltage dependence, activation of HCN channels is facilitated by direct binding of cAMP to a cyclic nucleotide-binding domain (CNBD) in the carboxyl-terminal region of each subunit. The CNBD is connected to the pore region via a gating ring formed from the C-linker of each subunit. The binding of cAMP to the CNBD causes a conformational change in the C-linker and potentiation of the pore opening, which leads to a speeding of channel activation and a depolarizing shift in the voltage ...

show abstract

TRIP8b Splice Forms Act in Concert to Regulate the Localization and Expression of HCN1 Channels in CA1 Pyramidal Neurons

Cited by 70 publications

References 30 publications

Reelin Signaling Specifies the Molecular Identity of the Pyramidal Neuron Distal Dendritic Compartment

Reelin Signaling Specifies the Molecular Identity of the Pyramidal Neuron Distal Dendritic Compartment

Development of Dendritic Form and Function

Structure and stoichiometry of an accessory subunit TRIP8b interaction with hyperpolarization-activated cyclic nucleotide-gated channels

Contact Info

Product

Resources

About