CaMKII locally encodes L-type channel activity to signal to nuclear CREB in excitation–transcription coupling

Wheeler, Damian G.; Barrett, Curtis F.; Groth, Rachel D.; Safa, Parsa; Tsien, Richard W.

doi:10.1085/jgp1331oia2

Cited by 29 publications

(44 citation statements)

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“…for neuronal survival, plasticity and memory formation through activation of the transcription factor cAMP responsive element binding protein (CREB) (Dolmetsch et al, 2001;Wheeler et al, 2008).…”

Section: Mechanosensitive Transmembrane Receptorsmentioning

confidence: 99%

Mechanosensitive mechanisms in transcriptional regulation

Mammoto

Ingber

2012

Journal of Cell Science

342

291

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SummaryTranscriptional regulation contributes to the maintenance of pluripotency, self-renewal and differentiation in embryonic cells and in stem cells. Therefore, control of gene expression at the level of transcription is crucial for embryonic development, as well as for organogenesis, functional adaptation, and regeneration in adult tissues and organs. In the past, most work has focused on how transcriptional regulation results from the complex interplay between chemical cues, adhesion signals, transcription factors and their co-regulators during development. However, chemical signaling alone is not sufficient to explain how three-dimensional (3D) tissues and organs are constructed and maintained through the spatiotemporal control of transcriptional activities. Accumulated evidence indicates that mechanical cues, which include physical forces (e.g. tension, compression or shear stress), alterations in extracellular matrix (ECM) mechanics and changes in cell shape, are transmitted to the nucleus directly or indirectly to orchestrate transcriptional activities that are crucial for embryogenesis and organogenesis. In this Commentary, we review how the mechanical control of gene transcription contributes to the maintenance of pluripotency, determination of cell fate, pattern formation and organogenesis, as well as how it is involved in the control of cell and tissue function throughout embryogenesis and adult life. A deeper understanding of these mechanosensitive transcriptional control mechanisms should lead to new approaches to tissue engineering and regenerative medicine. IntroductionTissue and organ architecture are constructed as a result of the complex orchestration of various cell types that exhibit specific behaviors (e.g. growth, differentiation, migration and apoptosis) in specific locations at precise times during embryogenesis. Transcriptional programs confer and maintain cellular identity and functions that are necessary for the maturation of embryonic cells into terminally differentiated tissues or organs, as well as for stem cell fate switching throughout adult life. These behaviors are regulated by turning genes on and off in a highly spatiotemporally controlled manner, and this process is mediated at the level of gene transcription through the interplay between RNA polymerase II, various transcription factors and their co-regulators (Box 1). Whereas most studies on transcriptional regulation have focused on genetic or chemical control mechanisms of transcription, recent work suggests that mechanical forces (Box 2) are equally important regulators of transcriptional control in embryonic and adult tissues. In this Commentary, we review these new insights into cellular mechanotransduction, and discuss how mechanical cues influence transcriptional regulation to govern organogenesis and to ensure tissue maintenance throughout adult life.

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Section: Mechanosensitive Transmembrane Receptorsmentioning

confidence: 99%

Mechanosensitive mechanisms in transcriptional regulation

Mammoto

Ingber

2012

Journal of Cell Science

342

291

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“…37 SCG neurons were plated onto coverslips and cultured overnight. To induce depolarization, cells were washed with elevated potassium chloride (KCl) solution ranging from 40-90 mM for 15 seconds, then washed with 5 mMKCl solution for 45 seconds.…”

Section: Immunocytochemistrymentioning

confidence: 99%

Ca_V2 channel subtype expression in rat sympathetic neurons is selectively regulated by α₂δ subunits

Scott

Kammermeier

2017

Channels

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Type two voltage gated calcium (Ca V 2) channels are the primary mediators of neurotransmission at neuronal presynapses, but their function at neural soma is also important in regulating excitability. 1 Mechanisms that regulate Ca V 2 channel expression at synapses have been studied extensively, which motivated us to perform similar studies in the soma. Rat sympathetic neurons from the superior cervical ganglion (SCG) natively express Ca V 2.2 and Ca V 2.3. 2 We noted previously that heterologous expression of Ca V 2.1 but not Ca V 2.2 results in increased calcium current in SCG neurons. 3 In the present study, we extended these observations to show that both Ca V 2.1 and Ca V 2.3 expression resulted in increased calcium currents while Ca V 2.2 expression did not. Further, Ca V 2.1 could displace native Ca V 2.2 channels, but Ca V 2.3 expression could not. Heterologous expression of the individual accessory subunits a 2 d-1, a 2 d-2, a 2 d-3, or b4 alone failed to increase current density, suggesting that the calcium current ceiling when Ca V 2.2 was over-expressed was not due to lack of these subunits. Interestingly, introduction of recombinant a2d subunits produced surprising effects on displacement of native Ca V 2.2 by recombinant channels. Both a 2 d-1 and a 2 d-2 seemed to promote Ca V 2.2 displacement by recombinant channel expression, while a 2 d-3 appeared to protect Ca V 2.2 from displacement. Thus, we observe a selective prioritization of Ca V channel functional expression in neurons by specific a 2 d subunits. These data highlight a new function for a 2 d subtypes that could shed light on subtype selectivity of Ca V 2 membrane expression.

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“…CaMKII interacts with many types of Ca 2þ channels and transmitter receptors including L-type voltage-sensitive calcium channels (VSCCs) (Hudmon et al 2005;Wheeler et al 2008), T-type VSCCs (Welsby et al 2003), P/Q-type VSCCs (Jiang et al 2008), dopamine receptors (Liu et al 2009), muscarinic receptors (Guo et al 2010), and the NR2B subunit of NMDAR (Bayer et al 2001;Merrill et al 2005). This naturally leads to the hypothesis that opening of specific channels activates bound pools of CaM-KII via nanodomain Ca 2þ .…”

Section: Camkiimentioning

confidence: 99%

Studying Signal Transduction in Single Dendritic Spines

Yasuda

2012

Cold Spring Harbor Perspectives in Biology

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CaMKII locally encodes L-type channel activity to signal to nuclear CREB in excitation–transcription coupling

Cited by 29 publications

References 1 publication

Mechanosensitive mechanisms in transcriptional regulation

Mechanosensitive mechanisms in transcriptional regulation

Ca_V2 channel subtype expression in rat sympathetic neurons is selectively regulated by α₂δ subunits

Studying Signal Transduction in Single Dendritic Spines

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CaMKII locally encodes L-type channel activity to signal to nuclear CREB in excitation–transcription coupling

Cited by 29 publications

References 1 publication

Mechanosensitive mechanisms in transcriptional regulation

Mechanosensitive mechanisms in transcriptional regulation

CaV2 channel subtype expression in rat sympathetic neurons is selectively regulated by α2δ subunits

Studying Signal Transduction in Single Dendritic Spines

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Product

Resources

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Ca_V2 channel subtype expression in rat sympathetic neurons is selectively regulated by α₂δ subunits