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.

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Probing the Structure and Function of TMC1 in Sensory Hair Cells using Mutagenesis and Cysteine Modification

Biophysical Journal ◽

10.1016/j.bpj.2014.11.2770 ◽

2015 ◽

Vol 108 (2) ◽

pp. 506a

Author(s):

Xiao-Ping Liu ◽

Bifeng Pan ◽

Yukako Asai ◽

Kyoto Kurima ◽

Andrew J. Griffith ◽

...

Keyword(s):

Hair Cells ◽

Structure And Function ◽

Cysteine Modification ◽

Sensory Hair ◽

Sensory Hair Cells ◽

And Function

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Filling the Silent Void: Genetic Therapies for Hearing Impairment

Genetics Research International ◽

10.1155/2012/748698 ◽

2012 ◽

Vol 2012 ◽

pp. 1-9

Author(s):

Joel Sng ◽

Thomas Lufkin

Keyword(s):

Inner Ear ◽

Hearing Impairment ◽

Hair Cells ◽

Genetic Disorders ◽

Environmental Damage ◽

Inner Ear Development ◽

Sensory Hair Cells ◽

And Function ◽

Function Potential

The inner ear cytoarchitecture forms one of the most intricate and delicate organs in the human body and is vulnerable to the effects of genetic disorders, aging, and environmental damage. Owing to the inability of the mammalian cochlea to regenerate sensory hair cells, the loss of hair cells is a leading cause of deafness in humans. Millions of individuals worldwide are affected by the emotionally and financially devastating effects of hearing impairment (HI). This paper provides a brief introduction into the key role of genes regulating inner ear development and function. Potential future therapies that leverage on an improved understanding of these molecular pathways are also described in detail.

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Usher proteins in inner ear structure and function

Physiological Genomics ◽

10.1152/physiolgenomics.00135.2013 ◽

2013 ◽

Vol 45 (21) ◽

pp. 987-989 ◽

Cited By ~ 20

Author(s):

Zubair M. Ahmed ◽

Gregory I. Frolenkov ◽

Saima Riazuddin

Keyword(s):

Inner Ear ◽

Hair Cells ◽

Molecular Mechanisms ◽

Usher Syndrome ◽

Structure And Function ◽

Linkage Studies ◽

And Function ◽

Insight Into

Usher syndrome (USH) is a neurosensory disorder affecting both hearing and vision in humans. Linkage studies of families of USH patients, studies in animals, and characterization of purified proteins have provided insight into the molecular mechanisms of hearing. To date, 11 USH proteins have been identified, and evidence suggests that all of them are crucial for the function of the mechanosensory cells of the inner ear, the hair cells. Most USH proteins are localized to the stereocilia of the hair cells, where mechano-electrical transduction (MET) of sound-induced vibrations occurs. Therefore, elucidation of the functions of USH proteins in the stereocilia is a prerequisite to understanding the exact mechanisms of MET.

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A Rubisco-binding protein is required for normal pyrenoid number and starch sheath morphology inChlamydomonas reinhardtii

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1904587116 ◽

2019 ◽

Vol 116 (37) ◽

pp. 18445-18454 ◽

Cited By ~ 14

Author(s):

Alan K. Itakura ◽

Kher Xing Chan ◽

Nicky Atkinson ◽

Leif Pallesen ◽

Lianyong Wang ◽

...

Keyword(s):

Surface Area ◽

Structure And Function ◽

Binding Motif ◽

Starch Granules ◽

Wild Type ◽

Bisphosphate Carboxylase ◽

Biophysical Mechanism ◽

Mechanism Function ◽

And Function

A phase-separated, liquid-like organelle called the pyrenoid mediates CO2fixation in the chloroplasts of nearly all eukaryotic algae. While most algae have 1 pyrenoid per chloroplast, here we describe a mutant in the model algaChlamydomonasthat has on average 10 pyrenoids per chloroplast. Characterization of the mutant leads us to propose a model where multiple pyrenoids are favored by an increase in the surface area of the starch sheath that surrounds and binds to the liquid-like pyrenoid matrix. We find that the mutant’s phenotypes are due to disruption of a gene, which we call StArch Granules Abnormal 1 (SAGA1) because starch sheath granules, or plates, in mutants lacking SAGA1 are more elongated and thinner than those of wild type. SAGA1 contains a starch binding motif, suggesting that it may directly regulate starch sheath morphology. SAGA1 localizes to multiple puncta and streaks in the pyrenoid and physically interacts with the small and large subunits of the carbon-fixing enzyme Rubisco (ribulose-1,5-bisphosphate carboxylase/oxygenase), a major component of the liquid-like pyrenoid matrix. Our findings suggest a biophysical mechanism by which starch sheath morphology affects pyrenoid number and CO2-concentrating mechanism function, advancing our understanding of the structure and function of this biogeochemically important organelle. More broadly, we propose that the number of phase-separated organelles can be regulated by imposing constraints on their surface area.

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Recovery of structure and function of inner ear afferent synapses following kainic acid excitotoxicity

Hearing Research ◽

10.1016/s0378-5955(96)00188-8 ◽

1997 ◽

Vol 105 (1-2) ◽

pp. 65-76 ◽

Cited By ~ 38

Author(s):

Xiang-Yang Zheng ◽

Donald Henderson ◽

Bo-Hua Hu ◽

Sandra L. McFadden

Keyword(s):

Inner Ear ◽

Kainic Acid ◽

Structure And Function ◽

And Function

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Alterations in flight muscle ultrastructure and function in Drosophila tropomyosin mutants.

The Journal of Cell Biology ◽

10.1083/jcb.135.3.673 ◽

1996 ◽

Vol 135 (3) ◽

pp. 673-687 ◽

Cited By ~ 38

Author(s):

A J Kreuz ◽

A Simcox ◽

D Maughan

Keyword(s):

Amino Acid ◽

Power Output ◽

Flight Muscle ◽

Structure And Function ◽

Wild Type ◽

Muscle Tropomyosin ◽

Ultrastructure And Function ◽

And Function ◽

Net Power Output ◽

Current Report

Drosophila indirect flight muscle (IFM) contains two different types of tropomyosin: a standard 284-amino acid muscle tropomyosin, Ifm-TmI, encoded by the TmI gene, and two > 400 amino acid tropomyosins, TnH-33 and TnH-34, encoded by TmII. The two IFM-specific TnH isoforms are unique tropomyosins with a COOH-terminal extension of approximately 200 residues which is hydrophobic and rich in prolines. Previous analysis of a hypomorphic TmI mutant, Ifm(3)3, demonstrated that Ifm-TmI is necessary for proper myofibrillar assembly, but no null TmI mutant or TmII mutant which affects the TnH isoforms have been reported. In the current report, we show that four flightless mutants (Warmke et al., 1989) are alleles of TmI, and characterize a deficiency which deletes both TmI and TmII. We find that haploidy of TmI causes myofibrillar disruptions and flightless behavior, but that haploidy of TmII causes neither. Single fiber mechanics demonstrates that power output is much lower in the TmI haploid line (32% of wild-type) than in the TmII haploid line (73% of wild-type). In myofibers nearly depleted of Ifm-TmI, net power output is virtually abolished (< 1% of wild-type) despite the presence of an organized fibrillar core (approximately 20% of wild-type). The results suggest Ifm-TmI (the standard tropomyosin) plays a key role in fiber structure, power production, and flight, with reduced Ifm-TmI expression producing corresponding changes of IFM structure and function. In contrast, reduced expression of the TnH isoforms has an unexpectedly mild effect on IFM structure and function.

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Radixin deficiency causes deafness associated with progressive degeneration of cochlear stereocilia

The Journal of Cell Biology ◽

10.1083/jcb.200402007 ◽

2004 ◽

Vol 166 (4) ◽

pp. 559-570 ◽

Cited By ~ 95

Author(s):

Shin-ichiro Kitajiri ◽

Kanehisa Fukumoto ◽

Masaki Hata ◽

Hiroyuki Sasaki ◽

Tatsuya Katsuno ◽

...

Keyword(s):

Hair Cells ◽

Plasma Membranes ◽

Wild Type ◽

Cross Link ◽

Erm Proteins ◽

Hearing Ability ◽

Adult Mice ◽

Progressive Degeneration ◽

Sensory Hair Cells

Ezrin/radixin/moesin (ERM) proteins cross-link actin filaments to plasma membranes to integrate the function of cortical layers, especially microvilli. We found that in cochlear and vestibular sensory hair cells of adult wild-type mice, radixin was specifically enriched in stereocilia, specially developed giant microvilli, and that radixin-deficient (Rdx−/−) adult mice exhibited deafness but no obvious vestibular dysfunction. Before the age of hearing onset (∼2 wk), in the cochlea and vestibule of Rdx−/− mice, stereocilia developed normally in which ezrin was concentrated. As these Rdx−/− mice grew, ezrin-based cochlear stereocilia progressively degenerated, causing deafness, whereas ezrin-based vestibular stereocilia were maintained normally in adult Rdx−/− mice. Thus, we concluded that radixin is indispensable for the hearing ability in mice through the maintenance of cochlear stereocilia, once developed. In Rdx−/− mice, ezrin appeared to compensate for radixin deficiency in terms of the development of cochlear stereocilia and the development/maintenance of vestibular stereocilia. These findings indicated the existence of complicate functional redundancy in situ among ERM proteins.

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The microRNA-183/96/182 Cluster is Essential for Stereociliary Bundle Formation and Function of Cochlear Sensory Hair Cells

Scientific Reports ◽

10.1038/s41598-018-36894-z ◽

2018 ◽

Vol 8 (1) ◽

Cited By ~ 6

Author(s):

Ruishuang Geng ◽

David N Furness ◽

Chithra K Muraleedharan ◽

Jinsheng Zhang ◽

Alain Dabdoub ◽

...

Keyword(s):

Hair Cells ◽

Sensory Hair ◽

Sensory Hair Cells ◽

And Function

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The plant circadian clock influences rhizosphere community structure and function

10.1101/158576 ◽

2017 ◽

Cited By ~ 1

Author(s):

Charley J. Hubbard ◽

Marcus T. Brock ◽

Linda T.A. van Diepen ◽

Loïs Maignien ◽

Brent E. Ewers ◽

...

Keyword(s):

Community Structure ◽

Microbial Community ◽

Circadian Clock ◽

Structure And Function ◽

Plant Performance ◽

Wild Type ◽

Night Time ◽

History Of ◽

And Function ◽

Rhizosphere Community

AbstractPlants alter chemical and physical properties of soil, and thereby influence rhizosphere microbial community structure. The structure of microbial communities may in turn affect plant performance. Yet, outside of simple systems with pairwise interacting partners, the plant genetic pathways that influence microbial community structure remain largely unknown, as are the performance feedbacks of microbial communities selected by the host plant genotype. We investigated the role of the plant circadian clock in shaping rhizosphere community structure and function. We performed 16S rRNA gene sequencing to characterize rhizosphere bacterial communities of Arabidopsis thaliana between day and night time points, and tested for differences in community structure between wild-type (Ws) vs. clock mutant (toc1-21, ztl-30) genotypes. We then characterized microbial community function, by growing wild-type plants in soils with an overstory history of Ws, toc1-21 or ztl-30 and measuring plant performance. We observed that rhizosphere community structure varied between day and night time points, and clock misfunction significantly altered rhizosphere communities. Finally, wild-type plants germinated earlier and were larger when inoculated with soils having an overstory history of wild-type in comparison to clock mutant genotypes. Our findings suggest the circadian clock of the plant host influences rhizosphere community structure and function.

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In Silico Electrophysiology of Inner-Ear Mechanotransduction Channel TMC1 Models

10.1101/2021.09.17.460860 ◽

2021 ◽

Author(s):

Sanket Walujkar ◽

Jeffrey M Lotthammer ◽

Collin R Nisler ◽

Joseph C Sudar ◽

Angela Ballesteros ◽

...

Keyword(s):

Inner Ear ◽

Conformational Changes ◽

Hair Cells ◽

Head Movements ◽

Mechanical Stimuli ◽

Ion Conduction ◽

Sensory Hair Cells ◽

Activation Mechanisms ◽

Dynamics Simulations ◽

Molecular Components

Inner-ear sensory hair cells convert mechanical stimuli from sound and head movements into electrical signals during mechanotransduction. Identification of all molecular components of the inner-ear mechanotransduction apparatus is ongoing; however, there is strong evidence that TMC1 and TMC2 are pore-forming subunits of the complex. We present molecular dynamics simulations that probe ion conduction of TMC1 models built based on two different structures of related TMEM16 proteins. Unlike most channels, the TMC1 models do not show a central pore. Instead, simulations of these models in a membrane environment at various voltages reveal a peripheral permeation pathway that is exposed to lipids and that shows cation permeation at rates comparable to those measured in hair cells. Furthermore, our analyses suggest that TMC1 gating mechanisms involve protein conformational changes and tension-induced lipid-mediated pore widening. These results provide insights into ion conduction and activation mechanisms of hair-cell mechanotransduction channels essential for hearing and balance.

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