The Ankyrin Repeats of TRPV1 Bind Multiple Ligands and Modulate Channel Sensitivity

Lishko, Polina V.; Procko, Erik; Jin, Xiangshu; Phelps, Christopher B.; Gaudet, Rachelle

doi:10.1016/j.neuron.2007.05.027

Cited by 372 publications

(502 citation statements)

References 42 publications

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“…20 (C) Structure of the ankyrin repeats of TRPV1 bound to ATP (spheres). 7 (D) Model of a 24-repeat domain, such as that of ankyrin, with the arrows indicating the direction of the possible spring (based on ref. 49 ).…”

Section: Discussionmentioning

confidence: 99%

“…2C). 7 The palm surface of the TRPV1 repeats forms an atypical nucleotide binding pocket. Biochemical studies demonstrated that ATP and calmodulin bind competitively to the same site.…”

Section: Nih-pa Author Manuscriptmentioning

confidence: 99%

“…Recent work from my lab and others has taken a structural biology approach to elucidate the roles of these ankyrin repeats in TRP channel function. [4][5][6][7][8][9] The emerging structural and functional features of these TRP channel ankyrin repeats are the focus of this short review. …”

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confidence: 99%

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A primer on ankyrin repeat function in TRP channels and beyond

2008

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Transient Receptor Potential (TRP) channels are rapidly gaining attention as important receptors and transducers of diverse sensory and environmental cues. Recent progress in the field has provided new insights into the structure and function of the ankyrin repeat motifs present in the Nterminal cytosolic domain of many TRP channels. The topics addressed in this review include the structural features of canonical ankyrin repeats, new clues into the functions these repeats perform in cells, and how this information can be applied to develop further experiments on TRP channels and other proteins containing ankyrin repeats.TRP proteins form a large family of ion channels particularly important in animals from worms to man, with more than 30 members in mammals. 1 The founding family member, the Drosophila trp gene -named for the "transient receptor potential" phenotype its mutation causes in light perception by photoreceptors -was first cloned in 1989. 2 The functions assigned to TRP channels in physiology are constantly expanding. They are key transducers of sensory signals, and are generally important in sensing information about the environment in both neuronal and non-neuronal cells (see ref. 3 for comprehensive reviews). Some TRP channels are found in excitable cells of the sensory nervous system, while others are expressed in various other tissues and organs. TRP channels have been implicated in many physiological processes, including calcium and magnesium homeostasis, neuronal growth, temperature sensation and pain perception, to name a few. For example, TRPV1 senses painfully hot temperatures, low extracellular pH and the capsaicin of "hot" chili peppers, while TRPA1 senses many painful chemical stimuli, including the pungent compounds in wasabi and cinnamon. TRPV1 and TRPA1 are expressed in partially overlapping sets of nociceptor neurons that transmit pain signals to the brain.At a molecular level, TRP channels assemble as tetramers through a channel domain that spans the membrane six times and has sequence similarity to voltage-gated ion channels. TRP channels also have large N-and C-terminal cytosolic domains that flank the transmembrane channel domain. These cytosolic domains participate in channel gating and regulation and sense information about the cellular state -ion and metabolite levels, for example. The TRP channel family is divided into seven subfamilies based on sequence similarity 1 : TRPA (ankyrin), TRPC (canonical), TRPM (melastatin), TRPML (mucolipin), TRPP (polycystin), TRPV (vanilloid), and TRPN (NOMPC). Several of these subfamilies -TRPA, TRPC, TRPN and TRPV -have ankyrin repeat sequence motifs in their N-terminal cytosolic domains. Recent work from my lab and others has taken a structural biology approach to elucidate the roles of these ankyrin repeats in TRP channel function. [4][5][6][7][8][9] The emerging structural and functional features of these TRP channel ankyrin repeats are the focus of this short review. NIH Public Access Ankyrin repeats and their structureAnkyrin rep...

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Section: Discussionmentioning

confidence: 99%

“…2C). 7 The palm surface of the TRPV1 repeats forms an atypical nucleotide binding pocket. Biochemical studies demonstrated that ATP and calmodulin bind competitively to the same site.…”

Section: Nih-pa Author Manuscriptmentioning

confidence: 99%

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A primer on ankyrin repeat function in TRP channels and beyond

2008

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“…31 High frequency calcium fluxes at the membrane result from increased channel opening events alone. TRP channel opening frequency is reportedly controlled by PIP2 [59][60][61][62] and inhibited by calmodulin. 59,[63][64][65] Studying these proteins in context of growth factor-stimulated calcium influx and EMT may be of interest.…”

Section: Molecular Control Of Calcium Influxes Upon Induction Of Epitmentioning

confidence: 99%

Control of cell mechanics by RhoA and calcium fluxes during epithelial scattering

2016

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Epithelial tissues use adherens junctions to maintain tight interactions and coordinate cellular activities. Adherens junctions are remodeled during epithelial morphogenesis, including instances of epithelialmesenchymal transition, or EMT, wherein individual cells detach from the tissue and migrate as individual cells. EMT has been recapitulated by growth factor induction of epithelial scattering in cell culture. In culture systems, cells undergo a highly reproducible series of cell morphology changes, most notably cell spreading followed by cellular compaction and cell migration. These morphology changes are accompanied by striking actin rearrangements. The current evidence suggests that global changes in actomyosin-based cellular contractility, first a loss of contractility during spreading and its activation during cell compaction, are the main drivers of epithelial scattering. In this review, we focus on how spreading and contractility might be controlled during epithelial scattering. While we propose a central role for RhoA, which is well known to control cellular contractility in multiple systems and whose role in epithelial scattering is well accepted, we suggest potential roles for additional cellular systems whose role in epithelial cell biology has been less well documented. In particular, we propose critical roles for vesicle recycling, calcium channels, and calcium-dependent kinases.

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“…The short-chain versions of PI(4,5)P 2 and PI(4)P (containing 8-carbon tails in place of the naturally occurring fatty acids) were purchased from Avanti Polar Lipids, Inc. Phosphoinositides were solubilized in a Ca 2+ -free solution (containing, in mM: 130 NaCl, repeat domain was not observed (Lishko et al, 2007). The proximal C-terminal region appears to be positioned close to the bilayer-solution interface (Fig.…”

Section: Phosphoinositides and Polylysinementioning

confidence: 99%