Regulated vesicular trafficking of specific PCDH15 and VLGR1 variants in auditory hair cells

Marisa L Zallocchi, Duane Delimont, Daniel T. Meehan, Dominic E Cosgrove

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Usher syndrome is a genetically heterogeneous disorder characterized by hearing and balance dysfunction and progressive retinitis pigmentosa. Mouse models carrying mutations for the nine Usher-associated genes have splayed stereocilia, and some show delayed maturation of ribbon synapses suggesting these proteins may play different roles in terminal differentiation of auditory hair cells. The presence of the Usher proteins at the basal and apical aspects of the neurosensory epithelia suggests the existence of regulated trafficking through specific transport proteins and routes. Immature mouse cochleae and UB/OC-1 cells were used in this work to address whether specific variants of PCDH15 and VLGR1 are being selectively transported to opposite poles of the hair cells. Confocal colocalization studies between apical and basal vesicular markers and the different PCDH15 and VLGR1 variants along with sucrose density gradients and the use of vesicle trafficking inhibitors show the existence of Usher protein complexes in at least two vesicular subpools. The apically trafficked pool colocalized with the early endosomal vesicle marker, rab5, while the basally trafficked pool associated with membrane microdomains and SNAP25. Moreover, coimmunoprecipitation experiments between SNAP25 and VLGR1 show a physical interaction of these two proteins in organ of Corti and brain. Collectively, these findings establish the existence of a differential vesicular trafficking mechanism for specific Usher protein variants in mouse cochlear hair cells, with the apical variants playing a potential role in endosomal recycling and stereocilia development/maintenance, and the basolateral variants involved in vesicle docking and/or fusion through SNAP25-mediated interactions.

Original languageEnglish (US)
Pages (from-to)13841-13859
Number of pages19
JournalJournal of Neuroscience
Volume32
Issue number40
DOIs
StatePublished - Oct 3 2012

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Auditory Hair Cells
Stereocilia
Proteins
Usher Syndromes
Hearing Disorders
Membrane Microdomains
Organ of Corti
Retinitis Pigmentosa
Cochlea
Synapses
Sucrose
Carrier Proteins
Epithelium
Maintenance
Mutation
Brain
Genes

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Regulated vesicular trafficking of specific PCDH15 and VLGR1 variants in auditory hair cells. / Zallocchi, Marisa L; Delimont, Duane; Meehan, Daniel T.; Cosgrove, Dominic E.

In: Journal of Neuroscience, Vol. 32, No. 40, 03.10.2012, p. 13841-13859.

Research output: Contribution to journalArticle

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