title: An endoplasmic reticulum trafficking signal prevents surface expression of a voltage- and Ca2+-activated K+ channel splice variant.
abstract: Protein delivery to restricted plasma membrane domains is exquisitely regulated at different stages of the cell trafficking machinery. Traffic control involves the recognition of export/retention/retrieval signals in the endoplasmic reticulum (ER)/Golgi complex that will determine protein fate. A splice variant (SV), SV1, of the voltage- and Ca(2+)-activated K(+) channel alpha-subunit accumulates the channel in the ER, preventing its surface expression. We show that SV1 insert contains a nonbasic, hydrophobic retention/retrieval motif, CVLF, that does not interfere with proper folding and tetramerization of SV1. Localization of proteins in the ER by CVLF is independent of its position; originally, on the first internal loop, SV1 insert or CVLF perform equally well if placed at the middle or end of the alpha-subunit intracellular carboxyl terminus. Also, CVLF is able to restrict the traffic of an independently expressed transmembrane protein, beta 1-subunit. CVLF is present in proteins across species and in lower organisms. Thus, CVLF may have evolved to serve as a regulator of cellular traffic.
authors.affiliation: Department of Anesthesiology, University of California, Los Angeles, 90095, USA.
authors.forename: M M
authors.initials: MM
authors.lastname: Zarei
authors.forename: M
authors.initials: M
authors.lastname: Eghbali
authors.forename: A
authors.initials: A
authors.lastname: Alioua
authors.forename: M
authors.initials: M
authors.lastname: Song
authors.forename: H-G
authors.initials: HG
authors.lastname: Knaus
authors.forename: E
authors.initials: E
authors.lastname: Stefani
authors.forename: L
authors.initials: L
authors.lastname: Toro
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008969:Molecular Sequence Data; D024681:Potassium Channels, Calcium-Activated / Q000737:chemistry / Q000378:metabolism*; D017510:Protein Folding; D020033:Protein Isoforms; D021381:Protein Transport
chemical_list: D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D051036:Large-Conductance Calcium-Activated Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D020033:Protein Isoforms