ATP-2 Interacts with the PLAT Domain of LOV-1 and Is Involved in<i>Caenorhabditis elegans</i>Polycystin Signaling

Hu, Jinghua; Barr, Maureen M.

doi:10.1091/mbc.e04-09-0851

Cited by 61 publications

(51 citation statements)

References 53 publications

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“…Barr and colleagues reported that CeKLP-6 transports PKD-2, a transient receptor protein channel, in sensory neurons (Peden and Barr, 2005). PKD-2 is proposed to form a receptor and/or channel complex with LOV-1, in which the PLAT domain physically interacts with ATP-2, the  subunit of ATP synthase (Igarashi and Somlo, 2002;Hu and Barr, 2005). These findings suggest the involvement of CeKLP-6 in mitochondrial movements along the C. elegans sensory neurons, although we did not observe this.…”

Section: Discussionmentioning

confidence: 99%

KLP6: a newly identified kinesin that regulates the morphology and transport of mitochondria in neuronal cells

Tanaka

Sugiura

Ichishita

et al. 2011

Journal of Cell Science

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Mitochondria utilize diverse cytoskeleton-based mechanisms to control their functions and morphology. Here, we report a role for kinesin-like protein KLP6, a newly identified member of the kinesin family, in mitochondrial morphology and dynamics. An RNA interference screen using Caenorhabditis elegans led us to identify a C. elegans KLP-6 involved in maintaining mitochondrial morphology. We cloned a cDNA coding for a rat homolog of C. elegans KLP-6, which is an uncharacterized kinesin in vertebrates. A rat KLP6 mutant protein lacking the motor domain induced changes in mitochondrial morphology and significantly decreased mitochondrial motility in HeLa cells, but did not affect the morphology of other organelles. In addition, the KLP6 mutant inhibited transport of mitochondria during anterograde movement in differentiated neuro 2a cells. To date, two kinesins, KIF1Bα and kinesin heavy chain (KHC; also known as KIF5) have been shown to be involved in the distribution of mitochondria in neurons. Expression of the kinesin heavy chain/KIF5 mutant prevented mitochondria from entering into neurites, whereas both the KLP6 and KIF1Bα mutants decreased mitochondrial transport in axonal neurites. Furthermore, both KLP6 and KIF1Bα bind to KBP, a KIF1-binding protein required for axonal outgrowth and mitochondrial distribution. Thus, KLP6 is a newly identified kinesin family member that regulates mitochondrial morphology and transport.

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Section: Discussionmentioning

confidence: 99%

KLP6: a newly identified kinesin that regulates the morphology and transport of mitochondria in neuronal cells

Tanaka

Sugiura

Ichishita

et al. 2011

Journal of Cell Science

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“…By using cDNAs with or without a stop codon, we generated STAM-1A and HGRS-1 GFP-tagged or untagged constructs, respectively. For the pkd-2 promoter, a 1.3-kb genomic fragment upstream of the start codon was used (Hu and Barr, 2005). For the stam-1 promoter, a 1.5-kb genomic fragment upstream of the stam-1 start codon was used.…”

Section: Molecular Biology Techniquesmentioning

confidence: 99%

STAM and Hrs Down-Regulate Ciliary TRP Receptors

Wittekind

Barr

2007

MBoC

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Cilia are endowed with membrane receptors, channels, and signaling components whose localization and function must be tightly controlled. In primary cilia of mammalian kidney epithelia and sensory cilia of Caenorhabditis elegans neurons, polycystin-1 (PC1) and transient receptor polycystin-2 channel (TRPP2 or PC2), function together as a mechanosensory receptor-channel complex. Despite the importance of the polycystins in sensory transduction, the mechanisms that regulate polycystin activity and localization, or ciliary membrane receptors in general, remain poorly understood. We demonstrate that signal transduction adaptor molecule STAM-1A interacts with C. elegans LOV-1 (PC1), and that STAM functions with hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs) on early endosomes to direct the LOV-1-PKD-2 complex for lysosomal degradation. In a stam-1 mutant, both LOV-1 and PKD-2 improperly accumulate at the ciliary base. Conversely, overexpression of STAM or Hrs promotes the removal of PKD-2 from cilia, culminating in sensory behavioral defects. These data reveal that the STAM-Hrs complex, which down-regulates ligand-activated growth factor receptors from the cell surface of yeast and mammalian cells, also regulates the localization and signaling of a ciliary PC1 receptor-TRPP2 complex. INTRODUCTIONCilia are specialized organelles that function in motility (motile or nodal cilia) or sensation (sensory or primary cilia). Several human genetic diseases are linked to defects in cilia formation or function Badano et al., 2006). Ciliary assembly via intraflagellar transport (IFT) and sensory transduction capabilities are evolutionarily conserved . These sensory devices, recently referred to as "antennae" or "nanomachines," transduce a plethora of sensory stimuli and must be fine-tuned both temporally and spatially to execute their cellular functions (Marshall and Nonaka, 2006;Scholey and Anderson, 2006;Singla and Reiter, 2006). Significant advances have been made in understanding cilia biogenesis and the genetic basis of human ciliary disease. In contrast, little is known regarding how cilia perceive, integrate, and transduce multiple extracellular stimuli into precise developmental and physiological responses.Sensory cilia are best known for their roles in photoreception and olfaction, which require G protein-coupled receptors (GPCRs) on the ciliary membrane (Buck and Axel, 1991;Marszalek et al., 2000). Cilia also act in mechanosensory and osmotic capacities and require ciliary localization of transient receptor potential (TRP) ion channels (Tobin et al., 2002;Kim et al., 2003;Nauli et al., 2003). Recently, vertebrate cilia have been shown to mediate not only environmental inputs, but also the Hedgehog (Hh) developmental cue that triggers translocation of the Smoothened (Smo) GPCR into the cilium (May et al., 2005;Huangfu and Anderson, 2006). Vertebrate cilia also express the somatostatin receptor sst3, serotonin 5-HT 6 receptor, platelet-derived growth factor receptor ␣ (PDGFR ␣) and epidermal growth fa...

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“…Two previous studies of the PLAT domain of LOV-1 (the worm homolog of PC1) have implicated it as a protein binding scaffold in regulating mating behavior. 38,39 However, the overall domain structure and function of LOV-1 is very different to mammalian PC1, and the sequence identity of worm PLAT is low ( Figure 1B). In addition, there is no conservation of the calcium binding (DGD 3157 ), phosphorylation (RNS 3164 ), or internalization (YEIL 3123 ) motifs identified in this study.…”

Section: Discussionmentioning

confidence: 99%

The Polycystin-1, Lipoxygenase, and α-Toxin Domain Regulates Polycystin-1 Trafficking

Streets

Hounslow

et al. 2016

Journal of the American Society of Nephrology

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Mutations in polycystin-1 (PC1) give rise to autosomal dominant polycystic kidney disease, an important and common cause of kidney failure. Despite its medical importance, the function of PC1 remains poorly understood. Here, we investigated the role of the intracellular polycystin-1, lipoxygenase, and a-toxin (PLAT) signature domain of PC1 using nuclear magnetic resonance, biochemical, cellular, and in vivo functional approaches. We found that the PLAT domain targets PC1 to the plasma membrane in polarized epithelial cells by a mechanism involving the selective binding of the PLAT domain to phosphatidylserine and L-a-phosphatidylinositol-4-phosphate (PI4P) enriched in the plasma membrane. This process is regulated by protein kinase A phosphorylation of the PLAT domain, which reduces PI4P binding and recruits b-arrestins and the clathrin adaptor AP2 to trigger PC1 internalization. Our results reveal a physiological role for the PC1-PLAT domain in renal epithelial cells and suggest that phosphorylation-dependent internalization of PC1 is closely linked to its function in renal development and homeostasis.

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ATP-2 Interacts with the PLAT Domain of LOV-1 and Is Involved inCaenorhabditis elegansPolycystin Signaling

Cited by 61 publications

References 53 publications

KLP6: a newly identified kinesin that regulates the morphology and transport of mitochondria in neuronal cells

KLP6: a newly identified kinesin that regulates the morphology and transport of mitochondria in neuronal cells

STAM and Hrs Down-Regulate Ciliary TRP Receptors

The Polycystin-1, Lipoxygenase, and α-Toxin Domain Regulates Polycystin-1 Trafficking

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