title: The yeast Batten disease orthologue Btn1 controls endosome-Golgi retrograde transport via SNARE assembly.
abstract: The human Batten disease gene CLN3 and yeast orthologue BTN1 encode proteins of unclear function. We show that the loss of BTN1 phenocopies that of BTN2, which encodes a retromer accessory protein involved in the retrieval of specific cargo from late endosomes (LEs) to the Golgi. However, Btn1 localizes to Golgi and regulates soluble N-ethyl-maleimide sensitive fusion protein attachment protein receptor (SNARE) function to control retrograde transport. Specifically, BTN1 overexpression and deletion have opposing effects on phosphorylation of the Sed5 target membrane SNARE, on Golgi SNARE assembly, and on Golgi integrity. Although Btn1 does not interact physically with SNAREs, it regulates Sed5 phosphorylation by modulating Yck3, a palmitoylated endosomal kinase. This may involve modification of the Yck3 lipid anchor, as substitution with a transmembrane domain suppresses the deletion of BTN1 and restores trafficking. Correspondingly, deletion of YCK3 mimics that of BTN1 or BTN2 with respect to LE-Golgi retrieval. Thus, Btn1 controls retrograde sorting by regulating SNARE phosphorylation and assembly, a process that may be adversely affected in Batten Disease patients.
authors: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
authors: Rachel
authors: R
authors: Kama
authors: Vydehi
authors: V
authors: Kanneganti
authors: Christian
authors: C
authors: Ungermann
authors: Jeffrey E
authors: JE
authors: Gerst
mesh_terms: D000071797:Butyrophilins; D047389:Casein Kinase I; D011992:Endosomes / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism*; D006801:Humans; D008562:Membrane Glycoproteins / Q000502:physiology*; D018832:Molecular Chaperones / Q000502:physiology*; D009472:Neuronal Ceroid-Lipofuscinoses; D010766:Phosphorylation; D021381:Protein Transport; D050600:SNARE Proteins / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D015003:Yeasts
chemical_list: D000071797:Butyrophilins; C105199:CLN3 protein, human; D008562:Membrane Glycoproteins; D018832:Molecular Chaperones; D050600:SNARE Proteins; D029701:Saccharomyces cerevisiae Proteins; D047389:Casein Kinase I; C479667:YCK3 protein, S cerevisiae