Plastin 1 widens stereocilia by transforming actin filament packing from hexagonal to liquid.
With their essential role in inner ear function, stereocilia of sensory hair cells demonstrate the importance of cellular actin protrusions. Actin packing in stereocilia is mediated by cross-linkers of the plastin, fascin, and espin families. Although mice lacking espin (ESPN) have no vestibular or auditory function, we found that mice that either lacked plastin 1 (PLS1) or had nonfunctional fascin 2 (FSCN2) had reduced inner ear function, with double-mutant mice most strongly affected. Targeted mass spectrometry indicated that PLS1 was the most abundant cross-linker in vestibular stereocilia and the second most abundant protein overall; ESPN only accounted for ∼15% of the total cross-linkers in bundles. Mouse utricle stereocilia lacking PLS1 were shorter and thinner than wild-type stereocilia. Surprisingly, although wild-type stereocilia had random liquid packing of their actin filaments, stereocilia lacking PLS1 had orderly hexagonal packing. Although all three cross-linkers are required for stereocilia structure and function, PLS1 biases actin toward liquid packing, which allows stereocilia to grow to a greater diameter.
Oregon Hearing Research Center, Oregon Health and Science University, Portland, OR 97239.|Vollum Institute, Oregon Health and Science University, Portland, OR 97239.
Jocelyn F
http://orcid.org/0000-0002-3015-4081
JF
Krey
Laboratory of Cell Structure and Dynamics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD 20892.
Evan S
http://orcid.org/0000-0002-0043-6977
ES
Krystofiak
Oregon Hearing Research Center, Oregon Health and Science University, Portland, OR 97239.|Vollum Institute, Oregon Health and Science University, Portland, OR 97239.
Rachel A
RA
Dumont
Department of Special Education and Communication Disorders, University of Nebraska-Lincoln, Lincoln, NE 68583.
Sarath
http://orcid.org/0000-0002-4652-2002
S
Vijayakumar
Oregon Health and Science University-Portland State University School of Public Health, Oregon Health and Science University, Portland, OR 97239.|Graduate School of Dentistry, Kyung Hee University, Seoul 02447, Republic of Korea.
Dongseok
http://orcid.org/0000-0002-1552-4072
D
Choi
Centre for Cardiovascular and Metabolic Research, The Hull York Medical School, University of Hull, Hull HU6 7RX, England, UK.
Francisco
http://orcid.org/0000-0001-5435-6991
F
Rivero
Laboratory of Cell Structure and Dynamics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD 20892.
Bechara
http://orcid.org/0000-0002-2803-8700
B
Kachar
Department of Special Education and Communication Disorders, University of Nebraska-Lincoln, Lincoln, NE 68583.
Sherri M
http://orcid.org/0000-0001-5018-3659
SM
Jones
Oregon Hearing Research Center, Oregon Health and Science University, Portland, OR 97239 gillespp@ohsu.edu.|Vollum Institute, Oregon Health and Science University, Portland, OR 97239.
Peter G
http://orcid.org/0000-0002-9787-5860
PG
Barr-Gillespie
D008841:Actin Cytoskeleton / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics; D003432:Cross-Linking Reagents / Q000378:metabolism; D006198:Hair Cells, Auditory / Q000378:metabolism / Q000648:ultrastructure; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D040901:Proteomics; D012444:Saccule and Utricle / Q000378:metabolism / Q000503:physiopathology / Q000648:ultrastructure; D059547:Stereocilia / Q000378:metabolism* / Q000648:ultrastructure; D015854:Up-Regulation
D002352:Carrier Proteins; D003432:Cross-Linking Reagents; D008562:Membrane Glycoproteins; D008840:Microfilament Proteins; C026742:plastin; C020324:fascin