title: Cadherin 23-C Regulates Microtubule Networks by Modifying CAMSAP3's Function.
abstract: Cadherin-related 23 (CDH23) is an adhesive protein important for hearing and vision, while CAMSAP3/Marshalin is a microtubule (MT) minus-end binding protein that regulates MT networks. Although both CDH23 and CAMSAP3/Marshalin are expressed in the organ of Corti, and carry several protein-protein interaction domains, no functional connection between these two proteins has been proposed. In this report, we demonstrate that the C isoform of CDH23 (CDH23-C) directly binds to CAMSAP3/Marshalin and modifies its function by inhibiting CAMSAP3/Marshalin-induced bundle formation, a process that requires a tubulin-binding domain called CKK. We further identified a conserved N-terminal region of CDH23-C that binds to the CKK domain. This CKK binding motif (CBM) is adjacent to the domain that interacts with harmonin, a binding partner of CDH23 implicated in deafness. Because the human Usher Syndrome 1D-associated mutation, CDH23 R3175H, maps to the CBM, we created a matched mutation in mouse CDH23-C at R55H. Both in vivo and in vitro assays decreased the ability of CDH23-C to interact with CAMSAP3/Marshalin, indicating that the interaction between CDH23 and CAMSAP3/Marshalin plays a vital role in hearing and vision. Together, our data suggest that CDH23-C is a CAMSAP3/Marshalin-binding protein that can modify MT networks indirectly through its interaction with CAMSAP3/Marshalin.
authors.affiliation: Department of Otolaryngology - Head and Neck Surgery, Feinberg School of Medicine, Northwestern University, Chicago IL 60611, USA.
authors.forename: Satoe
authors.initials: S
authors.lastname: Takahashi
authors.affiliation: Department of Otolaryngology - Head and Neck Surgery, Feinberg School of Medicine, Northwestern University, Chicago IL 60611, USA.
authors.forename: Vincent J
authors.initials: VJ
authors.lastname: Mui
authors.affiliation: Department of Otolaryngology - Head and Neck Surgery, Feinberg School of Medicine, Northwestern University, Chicago IL 60611, USA.
authors.forename: Samuel K
authors.initials: SK
authors.lastname: Rosenberg
authors.affiliation: Department of Otolaryngology - Head and Neck Surgery, Feinberg School of Medicine, Northwestern University, Chicago IL 60611, USA.|Knowles Hearing Center, Northwestern University, Evanston, IL 60208, USA.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Homma
authors.affiliation: Department of Communication Sciences and Disorders, Northwestern University, Evanston, IL 60208, USA.|Knowles Hearing Center, Northwestern University, Evanston, IL 60208, USA.
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Cheatham
authors.affiliation: Department of Otolaryngology - Head and Neck Surgery, Feinberg School of Medicine, Northwestern University, Chicago IL 60611, USA.|Knowles Hearing Center, Northwestern University, Evanston, IL 60208, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Zheng
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D000070585:Cadherin Related Proteins; D015820:Cadherins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D006801:Humans; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008870:Microtubules / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D020125:Mutation, Missense
chemical_list: C442480:CDH23 protein, human; D000070585:Cadherin Related Proteins; D015820:Cadherins; C000608274:Camsap3 protein, human; C578015:Camsap3 protein, mouse; C499091:Cdh23 protein, mouse; D008869:Microtubule-Associated Proteins