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Craig Montell

Publications and source records attributed to Craig Montell.

34 records · Page 2Linked to original sources
PubMed2004

Rhodopsin kinase activity modulates the amplitude of the visual response in Drosophila.

A feature shared between Drosophila rhodopsin and nearly all other G protein-coupled receptors is agonist-dependent protein phosphorylation. Despite extensive analyses of Drosophila phototransduction, the identity and function of the rhodopsin kinase (RK) have been elusive. Here, we provide evidence that G protein-coupled receptor kinase 1 (GPRK1), which is most similar to the beta-adrenergic receptor kinases, G protein-coupled receptor kinase 2 (GRK2) and GRK3, is the fly RK. We show that GPRK1 is enriched in photoreceptor cells, associates with the major Drosophila rhodopsin, Rh1, and phosphorylates the receptor. As is the case with mammalian GRK2 and GRK3, Drosophila GPRK1 includes a C-terminal pleckstrin homology domain, which binds to phosphoinositides and the Gbetagamma subunit. To address the role of GPRK1, we generated transgenic flies that expressed higher and lower levels of RK activity. Those flies with depressed levels of RK activity displayed a light response with a much larger amplitude than WT. Conversely, the amplitude of the light response was greatly suppressed in transgenic flies expressing abnormally high levels of RK activity. These data point to an evolutionarily conserved role for GPRK1 in modulating the amplitude of the visual response.

Animals↗
PubMed2004

Light-dependent translocation of visual arrestin regulated by the NINAC myosin III.

The rhodopsin regulatory protein, visual arrestin, undergoes light-dependent trafficking in mammalian and Drosophila photoreceptor cells, though the mechanisms underlying these movements are poorly understood. In Drosophila, the movement of the visual arrestin, Arr2, functions in long-term adaptation and is dependent on interaction with phosphoinositides (PIs). However, the basis for the requirement for PIs for light-dependent shuttling was unclear. Here, we demonstrated that the dynamic trafficking of Arr2 into the phototransducing compartment, the rhabdomere, required the eye-enriched myosin III, NINAC. We showed that defects in ninaC resulted in a long-term adaptation phenotype similar to that which occurred in arr2 mutants. The interaction between Arr2 and NINAC was PI dependent and NINAC bound directly to PIs. These data demonstrate that the light-dependent translocation of Arr2 into the rhabdomeres requires PI-mediated interactions between Arr2 and the NINAC myosin III.

Adaptation, Ocular↗
PubMed2004

A lysosomal tetraspanin associated with retinal degeneration identified via a genome-wide screen.

The Drosophila visual system has provided a model to study phototransduction and retinal degeneration. To identify new candidate proteins that contribute to these processes, we conducted a genome-wide screen for genes expressed predominately in the eye, using DNA microarrays. This screen appeared to be comprehensive as it led to the identification of all 22 eye-enriched genes previously shown to function in phototransduction or implicated in retinal degeneration. In addition, we identified 93 eye-enriched genes whose roles have not been previously defined. One of the eye-enriched genes encoded a member of a large family of transmembrane proteins, referred to as tetraspanins. We created a null mutation in the eye-enriched tetraspanin, Sunglasses (Sun), which resulted in light-induced retinal degeneration. We found that the Sun protein was distributed primarily in lysosomes, and functioned in a long-known but poorly understood phenomenon of light-induced degradation of rhodopsin. We propose that lysosomal tetraspanins in mammalian cells may also function in the downregulation of rhodopsin and other G-protein-coupled receptors, in response to intense or prolonged agonist stimulation.

Amino Acid Sequence↗
PubMed2004

Molecular genetics of Drosophila TRP channels.

The Drosophila TRP channel has served as a genetic model for understanding the functions, modes of activation, subunit assembly and protein interactions of TRP proteins in an in vivo context. During the last few years, it has become clear that TRP associates with a macromolecular complex, the signalplex, which includes TRP and many other signalling proteins critical for phototransduction. The central protein in this assembly is the PDZ protein INAD. Association of target proteins with INAD is required for rapid termination of the photoresponse and for proper localization of signalling proteins, such as TRP. In addition, TRP is reciprocally required for localizing INAD, indicating that TRP functions as both an ion channel and a molecular anchor. The TRP superfamily is comprised of six subfamilies, each of which includes homologues in Drosophila. Due to the similarities between mammalian and Drosophila TRP channels, and the tractability of genetic approaches in the fruitfly, investigations are underway to characterize the roles of additional Drosophila TRP proteins. Thus, the fruitfly continues to provide a valuable in vivo model to characterize the functions, interacting partners and activation mechanisms of TRP-related proteins.

Animals↗
PubMed2003

A flagellar polycystin-2 homolog required for male fertility in Drosophila.

A common inherited cause of renal failure, autosomal dominant polycystic kidney disease results from mutations in either of two genes, PKD1 and PKD2, which encode polycystin-1 and polycystin-2, respectively. Polycystin-2 has distant homology to TRP cation channels and associates directly with polycystin-1. The normal functions of polycystins are poorly understood, although recent studies indicate that they are concentrated in the primary cilia of a variety of cell types. In this report we identified a polycystin-2 homolog in Drosophila melanogaster; this homolog localized to the distal tip of the sperm flagella. A targeted mutation in this gene, almost there (amo), caused nearly complete male sterility. The amo males produced and transferred normal amounts of motile sperm to females, but mutant sperm failed to enter the female sperm storage organs, a prerequisite for fertilization. The finding that Amo functions in sperm flagella supports a common and evolutionarily conserved role for polycystin-2 proteins in both motile and nonmotile axonemal-containing structures.

Amino Acid Sequence↗
PubMed2003

Mg2+ homeostasis: the Mg2+nificent TRPM chanzymes.

TRPM6 and TRPM7 are distinct from all other ion channels in that they are composed of linked channel and protein kinase domains. Recent studies demonstrate that these 'chanzymes' are essential for Mg(2+) homeostasis, which is critical for human health and cell viability.

Homeostasis↗
PubMed2003

Light adaptation through phosphoinositide-regulated translocation of Drosophila visual arrestin.

Photoreceptor cells adapt to bright or continuous light, although the molecular mechanisms underlying this phenomenon are incompletely understood. Here, we report a mechanism of light adaptation in Drosophila, which is regulated by phosphoinositides (PIs). We found that light-dependent translocation of arrestin was defective in mutants that disrupt PI metabolism or trafficking. Arrestin bound to PIP(3) in vitro, and mutation of this site delayed arrestin shuttling and resulted in defects in the termination of the light response, which is normally accelerated by prior exposure to light. Disruption of the arrestin/PI interaction also suppressed retinal degeneration caused by excessive endocytosis of rhodopsin/arrestin complexes. These findings indicate that light-dependent trafficking of arrestin is regulated by direct interaction with PIs and is required for light adaptation. Since phospholipase C activity is required for activation of Drosophila phototransduction, these data point to a dual role of PIs in phototransduction.

Adaptation, Ocular↗
PubMed2003

TRPM5 is a voltage-modulated and Ca(2+)-activated monovalent selective cation channel.

The TRPM subfamily of mammalian TRP channels displays unusually diverse activation mechanisms and selectivities. One member of this subfamily, TRPM5, functions in taste receptor cells and has been reported to be activated through G protein-coupled receptors linked to phospholipase C. However, the specific mechanisms regulating TRPM5 have not been described. Here, we demonstrate that TRPM5 is a monovalent-specific cation channel with a 23 pS unitary conductance. TRPM5 does not display constitutive activity. Rather, it is activated by stimulation of a receptor pathway coupled to phospholipase C and by IP(3)-mediated Ca(2+) release. Gating of TRPM5 was dependent on a rise in Ca(2+) because it was fully activated by Ca(2+). Unlike any previously described mammalian TRP channel, TRPM5 displayed voltage modulation and rapid activation and deactivation kinetics upon receptor stimulation. The most closely related protein, the Ca(2+)-activated monovalent-selective cation channel TRPM4b, also showed voltage modulation, although with slower relaxation kinetics than TRPM5. Taken together, the data demonstrate that TRPM5 and TRPM4b represent the first examples of voltage-modulated, Ca(2+)-activated, monovalent cation channels (VCAMs). The voltage modulation and rapid kinetics provide TRPM5 with an excellent set of properties for participating in signaling in taste receptors and other excitable cells.

Animals↗
PubMed2003

Thermosensation: hot findings make TRPNs very cool.

TRPV and TRPM proteins have been shown to form temperature-responsive cation channels that act in nociception. Recent work on the mouse ANKTM1 and Drosophila Painless proteins shows that members of a third TRP subfamily, TRPN, also function in thermosensation.

Animals↗
PubMed2003

International Union of Pharmacology. XLIII. Compendium of voltage-gated ion channels: transient receptor potential channels.

The transient receptor potential (TRP) proteins are six transmembrane-containing subunits that combine to form cation-selective ion channels. TRP channels are present in yeast, Drosophila, Caenorhabditis elegans, and mammals. They are widely distributed and sense local changes in stimuli ranging from light to temperature and osmolarity. Mammals contain at least 22 distinct genes encoding these ion channels. This summary article presents an overview of the molecular relationships among the TRP channels and a standard nomenclature for them, which is derived from the IUPHAR Compendium of Voltage-Gated Ion Channels. The complete Compendium, including data tables for each member of the TRP channel family, can be found at http://www.iuphar-db.org/iuphar-ic/.

Animals↗
PubMed2002

Defective proboscis extension response (DPR), a member of the Ig superfamily required for the gustatory response to salt.

Gustatory stimuli, such as sugar, induce a behavioral response in Drosophila that involves extension of the proboscis and consumption of the sugar-containing solution. Addition of salt to the sugar solution inhibits this behavioral response. However, the mechanisms and gene products involved in the salt aversion response have not been described. Here, we report the identification of a locus, defective proboscis extension response (dpr), that is required for salt aversion. dpr was expressed in a subset of primary neurons in the gustatory organs and encoded a protein with two Ig-like domains, a single putative transmembrane domain, and a short region C terminal to the transmembrane segment. In addition, DPR defines a large previously unknown group of > or =20 highly related Ig-containing proteins.

Animals↗
PubMed2002

The TRP channels, a remarkably functional family.

TRP cation channels display an extraordinary assortment of selectivities and activation mechanisms, some of which represent previously unrecognized modes for regulating ion channels. Moreover, the biological roles of TRP channels appear to be equally diverse and range from roles in pain perception to male aggression.

Animals↗
PubMedDate not supplied

The venerable inveterate invertebrate TRP channels.

The transient receptor potential (TRP) superfamily is subdivided into four main classes of cation channels, TRPC, TRPV, TRPM and TRPN, each of which includes members in worms, flies, mice and humans. While the biophysical features of many of the mammalian channels have been described, relatively little is known concerning the biological roles of these channels. Forward genetic screens in Drosophila melanogaster and Caenorhabditis elegans have led to the identification of the founding members of each of these four subfamilies. Moreover, phenotypic analyses of invertebrate mutants have contributed greatly to our understanding of the roles of TRP proteins. A recurring theme is that many of these proteins function in sensory signaling processes ranging from vision to olfaction, osmosensation, light touch, social feeding, and temperature- and mechanically-induced nociception. In addition, at least one invertebrate TRP protein is required for cell division. As many of these functions may be conserved among the mammalian TRPs, the invertebrate TRPs offer valuable genetic handles for characterizing the functions of these cation channels in vivo.

Animals↗