title: Plasma Membrane Targeting of Protocadherin 15 Is Regulated by the Golgi-Associated Chaperone Protein PIST.
abstract: Protocadherin 15 (PCDH15) is a core component of hair cell tip-links and crucial for proper function of inner ear hair cells. Mutations ofPCDH15gene cause syndromic and nonsyndromic hearing loss. At present, the regulatory mechanisms responsible for the intracellular transportation of PCDH15 largely remain unknown. Here we show that PIST, a Golgi-associated, PDZ domain-containing protein, interacts with PCDH15. The interaction is mediated by the PDZ domain of PIST and the C-terminal PDZ domain-binding interface (PBI) of PCDH15. Through this interaction, PIST retains PCDH15 in the trans-Golgi network (TGN) and reduces the membrane expression of PCDH15. We have previously showed that PIST regulates the membrane expression of another tip-link component, cadherin 23 (CDH23). Taken together, our finding suggests that PIST regulates the intracellular trafficking and membrane targeting of the tip-link proteins CDH23 and PCDH15.
authors.affiliation: Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, Shandong University School of Life Sciences, Jinan, Shandong 250100, China.
authors.forename: Hongyun
authors.identifier: 0000-0003-0943-5409
authors.initials: H
authors.lastname: Nie
authors.affiliation: Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, Shandong University School of Life Sciences, Jinan, Shandong 250100, China.
authors.forename: Yueyue
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Taishan Medical University, Tai'an, Shandong 271000, China.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Yin
authors.affiliation: Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, Shandong University School of Life Sciences, Jinan, Shandong 250100, China.
authors.forename: Huiren
authors.identifier: 0000-0003-2421-5279
authors.initials: H
authors.lastname: Cao
authors.affiliation: Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, Shandong University School of Life Sciences, Jinan, Shandong 250100, China.
authors.forename: Yanfei
authors.identifier: 0000-0002-4043-0967
authors.initials: Y
authors.lastname: Wang
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Wei
authors.identifier: 0000-0002-2784-7696
authors.initials: W
authors.lastname: Xiong
authors.affiliation: Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, Shandong University School of Life Sciences, Jinan, Shandong 250100, China.
authors.forename: Yushuang
authors.identifier: 0000-0002-9387-9450
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, Shandong University School of Life Sciences, Jinan, Shandong 250100, China.
authors.forename: Zhigang
authors.identifier: 0000-0003-0082-7297
authors.initials: Z
authors.lastname: Xu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D019556:COS Cells; D000070585:Cadherin Related Proteins; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000502:physiology*; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism*; D002645:Chickens; D002522:Chlorocebus aethiops; D006056:Golgi Apparatus / Q000235:genetics / Q000378:metabolism*; D000077614:Golgi Matrix Proteins; D057809:HEK293 Cells; D006801:Humans; D008565:Membrane Proteins / Q000502:physiology*; D026901:Membrane Transport Proteins; D051379:Mice; D011485:Protein Binding / Q000502:physiology; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C418976:CDHR15 protein, mouse; D000070585:Cadherin Related Proteins; D015820:Cadherins; D002352:Carrier Proteins; C434484:GOPC protein, human; D000077614:Golgi Matrix Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D011498:Protein Precursors