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PIST regulates the intracellular trafficking and plasma membrane expression of cadherin 23.

Xu Z, Oshima K, Heller S - BMC Cell Biol. (2010)

Bottom Line: 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.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.

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Affiliation: Department of Otolaryngology--Head & Neck Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA. xuzg@sdu.edu.cn

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.

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Retention of cadherin 23 by PIST in trans-golgi network in transfected COS-7 cells. A. Myc-tagged cadherin 23 localizes in the cytoplasm. B. In the presence of EGFP-tagged PIST, Myc-tagged cadherin 23 co-localizes with EGFP-PIST and a trans-golgi network marker golgin-97. Myc-cadherin 23 was stained with rabbit anti-cadherin 23 antibody and golgin-97 was stained with mouse anti-golgin-97 antibody. Scale bar, 20 μm.
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Figure 5: Retention of cadherin 23 by PIST in trans-golgi network in transfected COS-7 cells. A. Myc-tagged cadherin 23 localizes in the cytoplasm. B. In the presence of EGFP-tagged PIST, Myc-tagged cadherin 23 co-localizes with EGFP-PIST and a trans-golgi network marker golgin-97. Myc-cadherin 23 was stained with rabbit anti-cadherin 23 antibody and golgin-97 was stained with mouse anti-golgin-97 antibody. Scale bar, 20 μm.

Mentions: The retention of cadherin 23 by PIST was also observed in transfected CHO and COS-7 cells (data not shown). PIST has been shown to associate with trans-golgi network (TGN) in mammalian cells [14]. To explore whether PIST retains cadherin 23 in TGN, we stained transfected cells with an antibody against a TGN maker, glogin-97. When cotransfected in COS-7 cells, Myc-cadherin 23 co-localized with EGFP-PIST, as well as golgin-97 (Figure 5). Our data suggests that by binding to cadherin 23, PIST retains cadherin 23 in TGN, hence reduces its membrane expression.


PIST regulates the intracellular trafficking and plasma membrane expression of cadherin 23.

Xu Z, Oshima K, Heller S - BMC Cell Biol. (2010)

Retention of cadherin 23 by PIST in trans-golgi network in transfected COS-7 cells. A. Myc-tagged cadherin 23 localizes in the cytoplasm. B. In the presence of EGFP-tagged PIST, Myc-tagged cadherin 23 co-localizes with EGFP-PIST and a trans-golgi network marker golgin-97. Myc-cadherin 23 was stained with rabbit anti-cadherin 23 antibody and golgin-97 was stained with mouse anti-golgin-97 antibody. Scale bar, 20 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2967513&req=5

Figure 5: Retention of cadherin 23 by PIST in trans-golgi network in transfected COS-7 cells. A. Myc-tagged cadherin 23 localizes in the cytoplasm. B. In the presence of EGFP-tagged PIST, Myc-tagged cadherin 23 co-localizes with EGFP-PIST and a trans-golgi network marker golgin-97. Myc-cadherin 23 was stained with rabbit anti-cadherin 23 antibody and golgin-97 was stained with mouse anti-golgin-97 antibody. Scale bar, 20 μm.
Mentions: The retention of cadherin 23 by PIST was also observed in transfected CHO and COS-7 cells (data not shown). PIST has been shown to associate with trans-golgi network (TGN) in mammalian cells [14]. To explore whether PIST retains cadherin 23 in TGN, we stained transfected cells with an antibody against a TGN maker, glogin-97. When cotransfected in COS-7 cells, Myc-cadherin 23 co-localized with EGFP-PIST, as well as golgin-97 (Figure 5). Our data suggests that by binding to cadherin 23, PIST retains cadherin 23 in TGN, hence reduces its membrane expression.

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Otolaryngology--Head & Neck Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA. xuzg@sdu.edu.cn

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.

Show MeSH
Related in: MedlinePlus