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Open Access Research article

PIST regulates the intracellular trafficking and plasma membrane expression of Cadherin 23

Zhigang Xu12*, Kazuo Oshima1 and Stefan Heller1

Author Affiliations

1 Departments of Otolaryngology - Head & Neck Surgery and Molecular & Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA

2 Key Laboratory for Experimental Teratology of the Ministry of Education, Institute of Developmental Biology, School of Life Sciences, Shandong University, Jinan, Shandong 250100, China

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BMC Cell Biology 2010, 11:80  doi:10.1186/1471-2121-11-80

Published: 19 October 2010

Abstract

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.