GPSM2-GNAI Specifies the Tallest Stereocilia and Defines Hair Bundle Row Identity
| Autor: | Abigail L.D. Tadenev, Nicholas Devanney, Jun Yang, Basile Tarchini, Anil Akturk, Pranav Dinesh Mathur, Anna M. Clark |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Mutant Cell Cycle Proteins Biology Article General Biochemistry Genetics and Molecular Biology Stereocilia EPS8 Mice 03 medical and health sciences 0302 clinical medicine Molecular level medicine Animals Humans Inner ear Hair Cells Auditory Inner Cell biology HEK293 Cells 030104 developmental biology medicine.anatomical_structure Bundle sense organs Hair cell GTP-Binding Protein alpha Subunit Gi2 General Agricultural and Biological Sciences Transduction (physiology) Row 030217 neurology & neurosurgery |
| Zdroj: | Current Biology. 29:921-934.e4 |
| ISSN: | 0960-9822 |
| DOI: | 10.1016/j.cub.2019.01.051 |
| Popis: | Summary The transduction compartment of inner ear hair cells, the hair bundle, is composed of stereocilia rows of graded height, a property essential for sensory function that remains poorly understood at the molecular level. We previously showed that GPSM2-GNAI is enriched at stereocilia distal tips and required for their postnatal elongation and bundle morphogenesis—two characteristics shared with MYO15A (short isoform), WHRN, and EPS8 proteins. Here we first performed a comprehensive genetic analysis of the mouse auditory epithelium to show that GPSM2, GNAI, MYO15A, and WHRN operate in series within the same pathway. To understand how these functionally disparate proteins act as an obligate complex, we then systematically analyzed their distribution in normal and mutant bundles over time. We discovered that WHRN-GPSM2-GNAI is an extra module recruited by and added to a pre-existing MYO15A-EPS8 stereocilia tip complex. This extended complex is only present in the first, tallest row, and is required to stabilize larger amounts of MYO15A-EPS8 than in shorter rows, which at tips harbor only MYO15A-EPS8. In the absence of GPSM2 or GNAI function, including in the epistatic Myo15a and Whrn mutants, bundles retain an embryonic-like organization that coincides with generic stereocilia at the molecular level. We propose that GPSM2-GNAI confers on the first row its unique tallest identity and participates in generating differential row identity across the hair bundle. |
| Databáze: | OpenAIRE |
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