A secretory-type protein, containing a pentraxin domain, interacts with an A-type K+ channel.

University of South Florida, Department of Otolaryngology, Head and Neck Surgery, Tampa, Florida 33612, USA.
Journal of Biological Chemistry (Impact Factor: 4.65). 05/2005; 280(15):15165-72. DOI: 10.1074/jbc.M500111200
Source: PubMed

ABSTRACT A-type K(+) channels belonging to the Shal subfamily are found in various receptor and neuronal cells. Although their kinetics and cell surface expression are regulated by auxiliary subunits, little is known about the proteins that may interact with Kv4 during development. A yeast two-hybrid screening of a cDNA library made from the sensory epithelium of embryonic chick cochlea revealed a novel association of Kv4.2 with a protein containing a pentraxin domain (PPTX). Sequence analysis shows that PPTX is a member of the long pentraxin family, is 53% identical to mouse PTX3, and has a signal peptide at the N terminus. Studies with chick cochlear tissues reveal that Kv4.2 coprecipitates PPTX and that both proteins are colocalized to the sensory and ganglion cells. A yeast two-hybrid assay demonstrated that the last 22 amino acids of the PPTX C terminus interact with the N terminus of Kv4.2. Chinese hamster ovary cells transfected with recombinant PPTX reveal secretory products in both non-truncated and truncated forms. Among the secreted variants are several blocked by Brefeldin A, suggesting export via a classical pathway. PPTX is soluble in the presence of sodium carbonate, suggesting localization to the cytosolic side of the plasmalemma. Immunohistochemical studies show that Kv4.2 and PPTX colocalize in the region of the plasmalemma of Chinese hamster ovary cells; however, both are locked in the endoplasmic reticulum of COS-7 cells, suggesting that PPTX does not act as a shuttle protein. Reverse transcription-PCR demonstrates that PPTX mRNA is found in tissues that include brain, eye, heart, and blood vessels.

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    10/2011; , ISBN: 978-953-307-281-4
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    ABSTRACT: Coordinated cardiac ion channel gating is fundamental for generation of action potential and excitability throughout the myocardium. The interaction of pore-forming ion channels with auxiliary subunits can regulate surface expression, localization and anchoring of these channels to plasma membrane. SNARE (soluble N-ethylmaleimide sensitive factors attachment protein or SNAP receptor) proteins mediate the targeting, docking, and fusion of intracellular vesicles for exocytotic release of neurotransmitters and hormones. In secretory neurons and neuroendocrine cells, some voltage-gated channels are physically coupled with SNARE proteins, resulting in alterations in channel gating and trafficking. Coupling of SNARE proteins to membrane ion channels is however not unique to secretory cells. We have demonstrated the expression of SNARE proteins in rodent myocardial tissue, and more importantly, functional interaction of SNARE proteins with cardiac K(ATP) and K(v) (K(v)1.2, K(v)2.1, K(v)4.2, K(v)4.3, and K(v)11.1) channels. SNARE proteins, therefore, have similar fundamental functions in ion channel trafficking and regulation per se, independent of secretion. We now review the body of work of SNARE protein regulation on membrane ion channels in the heart.
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    ABSTRACT: The transduction of sound by the receptor or hair cells of the cochlea leads to the activation of ion channels found in the basal and lateral regions of these cells. Thus, the processing of these transduced signals to the central nervous system is tied to the regulation of baso-lateral ion channels. The large conductance calcium-activated potassium or BK channel was revealed to interact with the small GTPase, Rab11b, which is one of many Rabs found in various endosomal pathways. Immunoelectron microscopy showed the colocalization of these two proteins in receptor cells and auditory neurons. Using Chinese hamster ovary cells as a heterologous expression system, Rab11b increased or decreased BK expression, depending on the overexpression or RNAi knockdown of Rab, respectively. Additional mutation analyses, using a yeast two-hybrid assay, suggested that this GTPase moderately interacts within a region of BK exclusive of the N- or C-terminal tails. These data suggest that this small GTPase regulates BK in a slow recycling process through the endocytic compartment and to the plasmalemma.
    Biochemical and Biophysical Research Communications 08/2012; 426(2):221-5. · 2.41 Impact Factor


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