Cadherin 23-C Regulates Microtubule Networks by Modifying CAMSAP3's Function.
Cadherin 23-C Regulates Microtubule Networks by Modifying CAMSAP3's Function.
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DOI：
10.1038/srep28706
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发表时间：
2016-06-28
影响因子：
4.6
通讯作者：
Zheng J
中科院分区：
文献类型：
--
作者：
Takahashi S;Mui VJ;Rosenberg SK;Homma K;Cheatham MA;Zheng J
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.
