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PMID:15272007

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Citation

Malhotra, JD, Thyagarajan, V, Chen, C and Isom, LL (2004) Tyrosine-phosphorylated and nonphosphorylated sodium channel beta1 subunits are differentially localized in cardiac myocytes. J. Biol. Chem. 279:40748-54

Abstract

Voltage-gated sodium channel alpha and beta subunits expressed in mammalian heart are differentially localized to t-tubules and intercalated disks. Sodium channel beta subunits are multifunctional molecules that participate in channel modulation and cell adhesion. Reversible, receptor-mediated changes in beta1 tyrosine phosphorylation modulate its ability to recruit and associate with ankyrin. The purpose of the present study was to test our hypothesis that tyrosine-phosphorylated beta1 (pYbeta1) and nonphosphorylated beta1 subunits may be differentially localized in heart and thus interact with different cytoskeletal and signaling proteins. We developed an antibody that specifically recognizes pYbeta1 and investigated the differential subcellular localization of beta1 and pYbeta1 in mouse ventricular myocytes. We found that pYbeta1 colocalized with connexin-43, N-cadherin, and Nav1.5 at intercalated disks but was not detected at the t-tubules. Anti-pYbeta1 immunoprecipitates N-cadherin from heart membranes and from cells transfected with beta1 and N-cadherin in the absence of other sodium channel subunits. pYbeta1 does not associate with ankyrinB in heart membranes. N-cadherin and connexin-43 associate with Nav1.5 in heart membranes as assessed by co-immunoprecipitation assays. We propose that sodium channel complexes at intercalated disks of ventricular myocytes are composed of Nav1.5 and pYbeta1 and that these complexes are in close association with both N-cadherin and connexin-43. beta1 phosphorylation appears to regulate its localization to differential subcellular domains.

Links

PubMed Online version:10.1074/jbc.M407243200

Keywords

Animals; Ankyrins/metabolism; Cadherins/chemistry; Cadherins/metabolism; Cell Line; Cells, Cultured; Connexin 43/metabolism; Cricetinae; Cytoskeleton/chemistry; DNA, Complementary/metabolism; Immunohistochemistry; Mice; Mice, Inbred C57BL; Muscle Proteins/chemistry; Myocardium/metabolism; Myocytes, Cardiac/metabolism; Phosphorylation; Phosphotyrosine/chemistry; Precipitin Tests; Protein Binding; Sodium Channels/chemistry; Transfection; Tyrosine/chemistry; Tyrosine/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:SCN1A

part_of

GO:0034706: sodium channel complex

ECO:0000353: physical interaction evidence used in manual assertion

PR:P97952
PR:Q9JJV9
UniProtKB:Q9WTU3

C

  • part_of:(CL:0000746)
  • part_of:(EMAPA:32748)

Seeded From UniProt

complete

MOUSE:CADH2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:Q9JJV9

F

  • occurs_in:(CL:0000746)
  • occurs_in:(EMAPA:32748)

Seeded From UniProt

complete

MOUSE:CXA1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:P97952
PR:Q9JJV9

F

  • occurs_in:(CL:0000746)
  • occurs_in:(EMAPA:32748)

Seeded From UniProt

complete

MOUSE:CXA1

located_in

GO:0014704: intercalated disc

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(CL:0000746)
  • part_of:(EMAPA:32748)

Seeded From UniProt

complete

MOUSE:SCN1B

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:P15116
PR:Q8C8R3

F

  • occurs_in:(CL:0000746)
  • occurs_in:(EMAPA:32748)

Seeded From UniProt

complete

MOUSE:SCN1B

located_in

GO:0014704: intercalated disc

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(CL:0000746)
  • part_of:(EMAPA:32748)

Seeded From UniProt

complete

MOUSE:SCN1B

located_in

GO:0030315: T-tubule

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(CL:0000746)
  • part_of:(EMAPA:32748)

Seeded From UniProt

complete

MOUSE:SCN1B

part_of

GO:0034706: sodium channel complex

ECO:0000353: physical interaction evidence used in manual assertion

PR:Q9JJV9
UniProtKB:A2APX8
UniProtKB:Q9WTU3

C

  • part_of:(CL:0000746)
  • part_of:(EMAPA:32748)

Seeded From UniProt

complete

MOUSE:ANK2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:P97952

F

  • occurs_in:(CL:0000746)
  • occurs_in:(EMAPA:32748)

Seeded From UniProt

complete

MOUSE:SCN5A

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:P15116
PR:Q8C8R3

F

Seeded From UniProt

complete

MOUSE:SCN5A

located_in

GO:0014704: intercalated disc

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(CL:0000746)
  • part_of:(EMAPA:32748)

Seeded From UniProt

complete

MOUSE:SCN5A

part_of

GO:0034706: sodium channel complex

ECO:0000353: physical interaction evidence used in manual assertion

PR:P97952
UniProtKB:A2APX8
UniProtKB:Q9WTU3

C

  • part_of:(CL:0000746)
  • part_of:(EMAPA:32748)

Seeded From UniProt

complete

MOUSE:SCN8A

part_of

GO:0034706: sodium channel complex

ECO:0000353: physical interaction evidence used in manual assertion

PR:P97952
PR:Q9JJV9
UniProtKB:A2APX8

C

  • part_of:(CL:0000746)
  • part_of:(EMAPA:32748)

Seeded From UniProt

complete

MOUSE:CXA1

part_of

GO:0014704: intercalated disc

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(EMAPA:32748)
  • part_of:(CL:0000746)

Seeded From UniProt

complete

MOUSE:Q68V28

part_of

GO:0034706: sodium channel complex

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P97952
UniProtKB:Q9JJV9
UniProtKB:Q9WTU3

C

  • part_of:(EMAPA:32748)
  • part_of:(CL:0000746)

Seeded From UniProt

complete


See also

References

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