Identification of a Cytoplasmic Domain Important in the Polarized Expression and Clustering of the Kv2.1 K+ Channel

Overview

Journal J Cell Biol

Specialty Cell Biology

Date 1996 Dec 1

PMID 8978827

Citations 64

Authors

R H Scannevin

H Murakoshi

K J Rhodes

J S Trimmer

Affiliations

Soon will be listed here.

Abstract

The voltage-sensitive K+ channel Kv2.1 has a polarized and clustered distribution in neurons. To investigate the basis for this localization, we expressed wild-type Kv2.1 and two COOH-terminal truncation mutants, delta C318 and delta C187, in polarized epithelial MDCK cells. These functional channel proteins had differing subcellular localization, in that while both wild-type Kv2.1 and delta C187 localized to the lateral membrane in high density clusters, delta C318 was expressed uniformly on both apical and lateral membranes. A chimeric protein containing the hemagglutinin protein from influenza virus and the region of Kv2.1 that differentiates the two truncation mutants (amino acids 536-666) was also expressed in MDCK cells, where it was found in high density clusters similar to those observed for Kv2.1. Polarized expression and clustering of Kv2.1 correlates with detergent solubility, suggesting that interaction with the detergent insoluble cytoskeleton may be necessary for proper localization of this channel.

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References

Compton T, Ivanov I, Gottlieb T, Rindler M, Adesnik M, Sabatini D . A sorting signal for the basolateral delivery of the vesicular stomatitis virus (VSV) G protein lies in its luminal domain: analysis of the targeting of VSV G-influenza hemagglutinin chimeras. Proc Natl Acad Sci U S A. 1989; 86(11):4112-6. PMC: 287399. DOI: 10.1073/pnas.86.11.4112. View

Niethammer M, Kim E, Sheng M . Interaction between the C terminus of NMDA receptor subunits and multiple members of the PSD-95 family of membrane-associated guanylate kinases. J Neurosci. 1996; 16(7):2157-63. PMC: 6578538. View

Nelson W, Shore E, Wang A, Hammerton R . Identification of a membrane-cytoskeletal complex containing the cell adhesion molecule uvomorulin (E-cadherin), ankyrin, and fodrin in Madin-Darby canine kidney epithelial cells. J Cell Biol. 1990; 110(2):349-57. PMC: 2116020. DOI: 10.1083/jcb.110.2.349. View

Dotti C, Simons K . Polarized sorting of viral glycoproteins to the axon and dendrites of hippocampal neurons in culture. Cell. 1990; 62(1):63-72. DOI: 10.1016/0092-8674(90)90240-f. View

VanDongen A, Frech G, Drewe J, Joho R, Brown A . Alteration and restoration of K+ channel function by deletions at the N- and C-termini. Neuron. 1990; 5(4):433-43. DOI: 10.1016/0896-6273(90)90082-q. View

Dotti C, Parton R, Simons K . Polarized sorting of glypiated proteins in hippocampal neurons. Nature. 1991; 349(6305):158-61. DOI: 10.1038/349158a0. View

Brewer C, Roth M . A single amino acid change in the cytoplasmic domain alters the polarized delivery of influenza virus hemagglutinin. J Cell Biol. 1991; 114(3):413-21. PMC: 2289095. DOI: 10.1083/jcb.114.3.413. View

Trimmer J . Immunological identification and characterization of a delayed rectifier K+ channel polypeptide in rat brain. Proc Natl Acad Sci U S A. 1991; 88(23):10764-8. PMC: 53011. DOI: 10.1073/pnas.88.23.10764. View

Sheng M, Tsaur M, Jan Y, Jan L . Subcellular segregation of two A-type K+ channel proteins in rat central neurons. Neuron. 1992; 9(2):271-84. DOI: 10.1016/0896-6273(92)90166-b. View

10.

Rodriguez Boulan E, Pendergast M . Polarized distribution of viral envelope proteins in the plasma membrane of infected epithelial cells. Cell. 1980; 20(1):45-54. DOI: 10.1016/0092-8674(80)90233-0. View

11.

Hamill O, Marty A, Neher E, Sakmann B, Sigworth F . Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Arch. 1981; 391(2):85-100. DOI: 10.1007/BF00656997. View

12.

Almers W, Stanfield P, Stuhmer W . Lateral distribution of sodium and potassium channels in frog skeletal muscle: measurements with a patch-clamp technique. J Physiol. 1983; 336:261-84. PMC: 1198969. DOI: 10.1113/jphysiol.1983.sp014580. View

13.

Pfeiffer S, Fuller S, Simons K . Development of cell surface polarity in the epithelial Madin-Darby canine kidney (MDCK) cell line. EMBO J. 1984; 3(11):2687-94. PMC: 557750. DOI: 10.1002/j.1460-2075.1984.tb02194.x. View

14.

Weiss R, Roberts W, Stuhmer W, Almers W . Mobility of voltage-dependent ion channels and lectin receptors in the sarcolemma of frog skeletal muscle. J Gen Physiol. 1986; 87(6):955-83. PMC: 2215866. DOI: 10.1085/jgp.87.6.955. View

15.

Doyle C, Sambrook J, Gething M . Analysis of progressive deletions of the transmembrane and cytoplasmic domains of influenza hemagglutinin. J Cell Biol. 1986; 103(4):1193-204. PMC: 2114346. DOI: 10.1083/jcb.103.4.1193. View

16.

Nelson W, Veshnock P . Dynamics of membrane-skeleton (fodrin) organization during development of polarity in Madin-Darby canine kidney epithelial cells. J Cell Biol. 1986; 103(5):1751-65. PMC: 2114393. DOI: 10.1083/jcb.103.5.1751. View

17.

Salas P, Gundersen D, Rodriguez-Boulan E . Formation of the apical pole of epithelial (Madin-Darby canine kidney) cells: polarity of an apical protein is independent of tight junctions while segregation of a basolateral marker requires cell-cell interactions. J Cell Biol. 1987; 104(4):905-16. PMC: 2114453. DOI: 10.1083/jcb.104.4.905. View

18.

Nelson W, Veshnock P . Modulation of fodrin (membrane skeleton) stability by cell-cell contact in Madin-Darby canine kidney epithelial cells. J Cell Biol. 1987; 104(6):1527-37. PMC: 2114506. DOI: 10.1083/jcb.104.6.1527. View

19.

Morrow J, Cianci C, Ardito T, Mann A, Kashgarian M . Ankyrin links fodrin to the alpha subunit of Na,K-ATPase in Madin-Darby canine kidney cells and in intact renal tubule cells. J Cell Biol. 1989; 108(2):455-65. PMC: 2115445. DOI: 10.1083/jcb.108.2.455. View

20.

Nelson W, Hammerton R . A membrane-cytoskeletal complex containing Na+,K+-ATPase, ankyrin, and fodrin in Madin-Darby canine kidney (MDCK) cells: implications for the biogenesis of epithelial cell polarity. J Cell Biol. 1989; 108(3):893-902. PMC: 2115384. DOI: 10.1083/jcb.108.3.893. View