Plastin 1 widens stereocilia by transforming actin filament packing from hexagonal to liquid

Abstract

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 crosslinkers of the plastin, fascin, and espin families. While mice lacking ESPN (espin) have no vestibular or auditory function, we found that mice that either lacked PLS1 (plastin 1) or had nonfunctional FSCN2 (fascin 2) had reduced inner-ear function, with double-mutant mice most strongly affected. Targeted mass spectrometry indicated that PLS1 was the most abundant crosslinker in vestibular stereocilia, and the second-most-abundant protein overall; ESPN only accounted for ~15% of the total crosslinkers in bundles. Mouse utricle stereocilia lacking PLS1 were shorter and thinner than wild-type stereocilia. Surprisingly, while wild-type stereocilia had random liquid packing of their actin filaments, stereocilia lacking PLS1 had orderly hexagonal packing. While all three crosslinkers are required for stereocilia structure and function, PLS1 biases actin towards liquid packing, which allows stereocilia to grow to a greater diameter