PIST regulates the intracellular trafficking and plasma membrane expression of cadherin 23.
BACKGROUND
The atypical cadherin protein cadherin 23 (CDH23) is crucial for proper function of retinal photoreceptors and inner ear hair cells. As we obtain more and more information about the specific roles of cadherin 23 in photoreceptors and hair cells, the regulatory mechanisms responsible for the transport of this protein to the plasma membrane are largely unknown.


RESULTS
PIST, a Golgi-associated, PDZ domain-containing protein, interacted with cadherin 23 via the PDZ domain of PIST and the C-terminal PDZ domain-binding interface (PBI) of cadherin 23. By binding to cadherin 23, PIST retained cadherin 23 in the trans-Golgi network of cultured cells. The retention was released when either of the two known cadherin 23-binding proteins MAGI-1 and harmonin was co-expressed. Similar to MAGI-1 and harmonin, PIST was detected in mouse inner ear sensory hair cells.


CONCLUSIONS
PIST binds cadherin 23 via its PDZ domain and retains cadherin 23 in trans-Golgi network. MAGI-1 and harmonin can compete with PIST for binding cadherin 23 and release cadherin 23 from PIST's retention. Our finding suggests that PIST, MAGI-1 and harmonin collaborate in intracellular trafficking of cadherin 23 and regulate the plasma membrane expression of cadherin 23.
Department of Otolaryngology--Head & Neck Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA. xuzg@sdu.edu.cn
Zhigang
Z
Xu
Kazuo
K
Oshima
Stefan
S
Heller
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D015820:Cadherins / Q000032:analysis / Q000378:metabolism*; D002352:Carrier Proteins / Q000032:analysis / Q000378:metabolism* / Q000502:physiology; D015815:Cell Adhesion Molecules; D018797:Cell Cycle Proteins; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins; D006056:Golgi Apparatus / Q000378:metabolism; D000077614:Golgi Matrix Proteins; D051528:Guanylate Kinases; D006199:Hair Cells, Auditory, Inner / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport
D048868:Adaptor Proteins, Signal Transducing; D015820:Cadherins; D002352:Carrier Proteins; C499091:Cdh23 protein, mouse; D015815:Cell Adhesion Molecules; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D000077614:Golgi Matrix Proteins; C435484:Gopc protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C492262:Ush1c protein, mouse; D051528:Guanylate Kinases; C493280:Magi1 protein, mouse