title: Elevation of Hook1 in a disease model of Batten disease does not affect a novel interaction between Ankyrin G and Hook1.
abstract: Hook1 is a member of a family of microtubule-binding proteins. Studies on the Drosophila homolog of Hook1 have suggested a role in the maturation and trafficking of internalized proteins to the late endosome. A weak interaction between Hook1 and the lysosomal/late endosomal protein, CLN3, was recently reported. Mutations in CLN3 result in the neurological disorder Batten disease. Here we show a novel interaction between Hook1 and Ankyrin G, an adaptor protein that binds the spectrin-actin cytoskeleton and targets proteins to the peripheral membrane. Although we demonstrate co-localization of Hook1 and Ankyrin G, Hook1 also localizes to additional regions of the cell devoid of Ankyrin G where it likely interacts with other proteins. There is no disruption of the Hook1-Ankyrin G interaction or localization in tissue derived from a Cln3-knockout mouse despite a nearly threefold increase in the expression of Hook1. However, mutation of CLN3 could lead to alterations in the functioning and positioning of organelles and membrane proteins through this Hook1-Ankyrin G interaction.
authors.affiliation: Center for Aging and Developmental Biology, Aab Institute of Biomedical Sciences, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
authors.forename: Jill M
authors.initials: JM
authors.lastname: Weimer
authors.forename: Subrata
authors.initials: S
authors.lastname: Chattopadhyay
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Custer
authors.forename: David A
authors.initials: DA
authors.lastname: Pearce
mesh_terms: D000818:Animals; D017487:Ankyrins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D009472:Neuronal Ceroid-Lipofuscinoses / Q000235:genetics / Q000378:metabolism*; D009900:Optic Nerve / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D020798:Two-Hybrid System Techniques
chemical_list: C094681:Ank3 protein, mouse; D017487:Ankyrins; C102229:CLN3 protein, mouse; D008562:Membrane Glycoproteins; D008869:Microtubule-Associated Proteins; D018832:Molecular Chaperones; D012333:RNA, Messenger; C471055:hook1 protein, human