title: Uncoordinated (UNC)119: coordinating the trafficking of myristoylated proteins.
abstract: The mechanism by which myristoylated proteins are targeted to specific subcellular membrane compartments is poorly understood. Two novel acyl-binding proteins, UNC119A and UNC119B, have been shown recently to function as chaperones/co-factors in the transport of myristoylated G protein α-subunits and src-type tyrosine kinases. UNC119 polypeptides feature an immunoglobulin-like β-sandwich fold that forms a hydrophobic pocket capable of binding lauroyl (C12) and myristoyl (C14) side chains. UNC119A in rod photoreceptors facilitates the transfer of transducin α subunits (Tα) from inner segment to outer segment membranes by forming an intermediate diffusible UNC119-Tα complex. Similar complexes are formed in other sensory neurons, as the G proteins ODR-3 and GPA-13 in Caenorhabditis elegans unc-119 mutants traffic inappropriately. UNC119B knockdown in IMCD3 cells prevents trafficking ofmyristoylated nephrocystin-3 (NPHP3), a protein associated with nephronophthisis, to cilia. Further, UNC119A was shown to transport myristoylated src-type tyrosine kinases to cell membranes and to affect T-cell receptor (TCR) and interleukin-5 receptor (IL-5R) activities. These interactions establish UNC119 polypeptides as novel lipid-binding chaperones with specificity for a diverse subset of myristoylated proteins.
authors.affiliation: Graduate Program in Neuroscience, University of Utah Health Science Center, Salt Lake City, UT 84132, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Constantine
authors.forename: Houbin
authors.initials: H
authors.lastname: Zhang
authors.forename: Cecilia D
authors.initials: CD
authors.lastname: Gerstner
authors.forename: Jeanne M
authors.initials: JM
authors.lastname: Frederick
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Baehr
mesh_terms: D000213:Acyl Carrier Protein / Q000737:chemistry / Q000502:physiology*; D000818:Animals; D017173:Caenorhabditis elegans / Q000502:physiology; D002923:Cilia / Q000502:physiology; D044385:GTP-Binding Protein alpha Subunits / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D018832:Molecular Chaperones / Q000502:physiology; D017434:Protein Structure, Tertiary; D021381:Protein Transport / Q000502:physiology; D017948:Retinal Rod Photoreceptor Cells / Q000502:physiology; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D000213:Acyl Carrier Protein; D044385:GTP-Binding Protein alpha Subunits; D047908:Intracellular Signaling Peptides and Proteins; D018832:Molecular Chaperones; D019061:src-Family Kinases