Adenylyl cyclase 6 plays a minor role in the mouse inner ear and retina

Pranav Dinesh Mathur; Junhuang Zou; Grace Neiswanger; Daniel Zhu; Yong Wang; Ali A Almishaal; Deepti Vashist; H Kirk Hammond; Albert H Park; Jun Yang

doi:10.1038/s41598-023-34361-y

Adenylyl cyclase 6 plays a minor role in the mouse inner ear and retina

Sci Rep. 2023 May 1;13(1):7075. doi: 10.1038/s41598-023-34361-y.

Authors

Pranav Dinesh Mathur^#^{1

2

3}, Junhuang Zou^#¹, Grace Neiswanger¹, Daniel Zhu¹, Yong Wang⁴, Ali A Almishaal^{5

6}, Deepti Vashist¹, H Kirk Hammond⁷, Albert H Park⁴, Jun Yang^{8

9

10}

Affiliations

¹ Department of Ophthalmology and Visual Sciences, Moran Eye Center, University of Utah, Salt Lake City, UT, 84132, USA.
² Department of Neurobiology, University of Utah, Salt Lake City, UT, 84132, USA.
³ Vecprobio Inc., San Diego, CA, 92126, USA.
⁴ Division of Otolaryngology, Department of Surgery, University of Utah, Salt Lake City, UT, 84132, USA.
⁵ Department of Communication Sciences and Disorders, University of Utah, Salt Lake City, UT, 84112, USA.
⁶ Department of Speech-Language Pathology and Audiology, College of Applied Medical Sciences, University of Hail, Hail, 81451, Saudi Arabia.
⁷ Division of Cardiovascular Medicine, Department of Medicine, University of California, San Diego, VA San Diego Healthcare System, San Diego, CA, 92161, USA.
⁸ Department of Ophthalmology and Visual Sciences, Moran Eye Center, University of Utah, Salt Lake City, UT, 84132, USA. jun.yang@hsc.utah.edu.
⁹ Department of Neurobiology, University of Utah, Salt Lake City, UT, 84132, USA. jun.yang@hsc.utah.edu.
¹⁰ Division of Otolaryngology, Department of Surgery, University of Utah, Salt Lake City, UT, 84132, USA. jun.yang@hsc.utah.edu.

^# Contributed equally.

Abstract

Adenylyl cyclase 6 (AC6) synthesizes second messenger cAMP in G protein-coupled receptor (GPCR) signaling. In cochlear hair cells, AC6 distribution relies on an adhesion GPCR, ADGRV1, which is associated with Usher syndrome (USH), a condition of combined hearing and vision loss. ADGRV1 is a component of the USH type 2 (USH2) protein complex in hair cells and photoreceptors. However, the role of AC6 in the inner ear and retina has not been explored. Here, we found that AC6 distribution in hair cells depends on the USH2 protein complex integrity. Several known AC6 regulators and effectors, which were previously reported to participate in ADGRV1 signaling in vitro, are localized to the stereociliary compartments that overlap with AC6 distribution in hair cells. In young AC6 knockout (Adcy6^-/-) mice, the activity of cAMP-dependent protein kinase, but not Akt kinase, is altered in cochleas, while both kinases are normal in vestibular organs. Adult Adcy6^-/- mice however exhibit normal hearing function. AC6 is expressed in mouse retinas but rarely in photoreceptors. Adcy6^-/- mice have slightly enhanced photopic but normal scotopic vision. Therefore, AC6 may participate in the ADGRV1 signaling in hair cells but AC6 is not essential for cochlear and retinal development and maintenance.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adenylyl Cyclases / metabolism
Animals
Hair Cells, Auditory / metabolism
Mice
Retina* / metabolism
Usher Syndromes*

Substances

adenylyl cyclase 6
Adenylyl Cyclases

Abstract

Publication types

MeSH terms

Substances

Grants and funding