RGS14 is a Microtubule-Associated Protein

Martin-McCaffrey, Luke; Willard, Francis S.; Pająk, Agnieszka; Dagnino, Lina; Siderovski, David P.; D’Souza, Sudhir J.A.

doi:10.4161/cc.4.7.1787

Cited by 32 publications

(33 citation statements)

References 65 publications

(74 reference statements)

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“…[25][26][27] Thus, tubulin PTMs may play a role in directing mitotic events including targeting of effector proteins to a subset of microtubules (for examples, see Refs. [124][125][126][127][128]. In support of this, increased levels of detyrosinated tubulin seen in fibroblasts cultured from TTL null mice resulted in defects in spindle orientation 82 and yeast cells expressing only detyrosinated a-tubulin displayed defects in nuclear positioning and spindle dynamics.…”

Section: Who Are the Interpreters Of The Tubulin Code?mentioning

confidence: 78%

The Tubulin Code

Verhey

Gaertig²

2007

Cell Cycle

482

393

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AbbreViAtions PTMposttranslational modification CTT C-terminal tail TTL tubulin tyrosine ligase TTLL TTL-like enzyme MAP microtubule associated protein +TIP plus-end tracking protein CLIP cytoplasmic linker protein AcKnowledGementsWe thank Marie-Helene Bré, David Allis, and Ray Trievel for stimulating discussions and reading the manuscript. Work in our labs is supported by the NSF (033965 to J.G.) and NIH (GM070862 to K.J.V.). AbstrActMicrotubules create diverse arrays with specific cellular functions such as the mitotic spindle, cilia and bundles inside neurons. How microtubules are regulated to enable specific functions is not well understood. Recent work has shown that posttranslational modifications of the tubulin building blocks mark subpopulations of microtubules and selectively affect downstream microtubule-based functions. In this way, the tubulin modifications generate a "code" that can be read by microtubule-associated proteins in a manner analogous to how the histone code directs diverse chromatin functions. Here we review recent progress in understanding how the tubulin code is generated, maintained, and read by microtubule effectors.

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Section: Who Are the Interpreters Of The Tubulin Code?mentioning

confidence: 78%

The Tubulin Code

Verhey

Gaertig²

2007

Cell Cycle

482

393

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“…65 A number of RGS proteins play specific roles in a receptor-independent, G protein-mediated process of mitosis and cell division. [70][71][72][73][74] Recent studies have demonstrated that RGS7 and the GoLoco domain-containing RGS14, via distinct mechanisms, specifically regulate microtubule dynamics, mitotic spindle formation and movements. 70-72 RGS7 appears to promote an asymmetric G protein function by playing dual roles as both the negative regulator and the effector for Gαo.…”

Section: Rgs Proteins Selectively Regulate Other G Protein-mediated Ementioning

confidence: 99%

How Regulators of G Protein Signaling Achieve Selective Regulation

Xie

Palmer

2007

Journal of Molecular Biology

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SummaryThe regulators of G protein signaling (RGS) are a family of cellular proteins that play an essential regulatory role in G protein-mediated signal transduction. There are multiple RGS subfamilies consisting of over twenty different RGS proteins. They are basically the guanosine triphosphatase (GTPase)-accelerating proteins that specifically interact with G protein α subunits. RGS proteins display remarkable selectivity and specificity in their regulation of receptors, ion channels, and other G protein-mediated physiological events. The molecular and cellular mechanisms underlying such selectivity are complex and cooperate at many different levels. Recent research data have provided strong evidence that the spatiotemporal-specific expression of RGS proteins and their target components, as well as the specific protein-protein recognition and interaction through their characteristic structural domains and functional motifs, are determinants for RGS selectivity and specificity. Other molecular mechanisms, such as alternative splicing and scaffold proteins, also significantly contribute to RGS selectivity. To pursue a thorough understanding of the mechanisms of RGS selective regulation will be of great significance for the advancement of our knowledge of molecular and cellular signal transduction.

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“…This SNP is intronic within RGS14 (regulator of G-protein signaling 14). 42 However, rs4074995 is in strong linkage disequilibrium (LD) with SNPs in the directly adjacent gene, SLC34A1 (solute carrier family 34 [type 2 sodium/ phosphate cotransporter], member 1). SLC34A1 is a strong candidate gene for PTH concentration, as it encodes the kidney-specific sodium-phosphate type 2a transporter (Npt2a) responsible for phosphate reabsorption in the proximal tubule.…”

mentioning

confidence: 99%

Genetic Variants Associated with Circulating Parathyroid Hormone

Robinson‐Cohen

Lutsey²,

Kleber

et al. 2016

JASN

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Parathyroid hormone (PTH) is a primary calcium regulatory hormone. Elevated serum PTH concentrations in primary and secondary hyperparathyroidism have been associated with bone disease, hypertension, and in some studies, cardiovascular mortality. Genetic causes of variation in circulating PTH concentrations are incompletely understood. We performed a genome-wide association study of serum PTH concentrations among 29,155 participants of European ancestry from 13 cohort studies (n=22,653 and n=6502 in discovery and replication analyses, respectively). We evaluated the association of single nucleotide polymorphisms (SNPs) with natural log-transformed PTH concentration adjusted for age, sex, season, study site, and principal components of ancestry. We discovered associations of SNPs from five independent regions with serum PTH concentration, including the strongest association with rs6127099 upstream of CYP24A1 (P=4.2 3 10 253 ), a gene that encodes the primary catabolic enzyme for 1,25-dihydroxyvitamin D and 25-dihydroxyvitamin D. Each additional copy of the minor allele at this SNP associated with 7% higher serum PTH concentration. The other SNPs associated with serum PTH concentration included rs4074995 within RGS14 (P=6.6 3 10 217 ), rs219779 adjacent to CLDN14 (P=3.5 3 10 216 ), rs4443100 near RTDR1 (P=8.7 3 10 29 ), and rs73186030 near CASR (P=4.8 3 10 28). Of these five SNPs, rs6127099, rs4074995, and rs219779 replicated. Thus, common genetic variants located near genes involved in vitamin D metabolism and calcium and renal phosphate transport associated with differences in circulating PTH concentrations. Future studies could identify the causal variants at these loci, and the clinical and functional relevance of these variants should be pursued.

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RGS14 is a Microtubule-Associated Protein

Cited by 32 publications

References 65 publications

The Tubulin Code

The Tubulin Code

How Regulators of G Protein Signaling Achieve Selective Regulation

Genetic Variants Associated with Circulating Parathyroid Hormone

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