Myosin motors in sensory hair bundle assembly

Moreland, Zane G.; Bird, Jonathan E.

doi:10.1016/j.ceb.2022.102132

Cited by 13 publications

(16 citation statements)

References 101 publications

(111 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…COX7A is part of the mitochondrial genes that were found altered in blood early in AD [ 34 ]. MYO15A is a myosin involved in actin organisation in mechanosensory hair bundles [ 35 ]. Although no direct link with the endosomal compartment has been found yet, the role of actin in retromer function is well described and retromer dysfunction is occurring in neurodegenerative disease including AD [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

Modifications of the endosomal compartment in fibroblasts from sporadic Alzheimer’s disease patients are associated with cognitive impairment

et al. 2023

View full text Add to dashboard Cite

Morphological alterations of the endosomal compartment have been widely described in post-mortem brains from Alzheimer’s disease (AD) patients and subjects with Down syndrome (DS) who are at high risk for AD. Immunostaining with antibodies against endosomal markers such as Early Endosome Antigen 1 (EEA1) revealed increased size of EEA1-positive puncta. In DS, peripheral cells such as peripheral blood mononuclear cells (PBMCs) and fibroblasts, share similar phenotype even in the absence of AD. We previously found that PBMCs from AD patients have larger EEA1-positive puncta, correlating with brain amyloid load. Here we analysed the endosomal compartment of fibroblasts from a very well characterised cohort of AD patients (IMABio3) who underwent thorough clinical, imaging and biomarkers assessments. Twenty-one subjects were included (7 AD with mild cognitive impairment (AD-MCI), 7 AD with dementia (AD-D) and 7 controls) who had amyloid-PET at baseline (PiB) and neuropsychological tests at baseline and close to skin biopsy. Fibroblasts isolated from skin biopsies were immunostained with anti-EEA1 antibody and imaged using a spinning disk microscope. Endosomal compartment ultrastructure was also analysed by electron microscopy. All fibroblast lines were genotyped and their AD risk factors identified. Our results show a trend to an increased EEA1-positive puncta volume in fibroblasts from AD-D as compared to controls (p.adj = 0.12) and reveal enhanced endosome area in fibroblasts from AD-MCI and AD-AD versus controls. Larger puncta size correlated with PiB retention in different brain areas and with worse cognitive scores at the time of biopsy as well as faster decline from baseline to the time of biopsy. Finally, we identified three genetic risk factors for AD (ABCA1, COX7C and MYO15A) that were associated with larger EEA1 puncta volume. In conclusion, the endosomal compartment in fibroblasts could be used as cellular peripheral biomarker for both amyloid deposition and cognitive decline in AD patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Modifications of the endosomal compartment in fibroblasts from sporadic Alzheimer’s disease patients are associated with cognitive impairment

et al. 2023

View full text Add to dashboard Cite

show abstract

“…MYL12 binds to unconventional myosins including MYO15A (Bird et al, 2014) and MYO7A, a myosin motor of cochlear hair cells (Sakai et al, 2015). Both of these unconventional myosins possess IQ motifs to which their light chains bind (Moreland & Bird, 2022). MYO1C also has IQ motifs that bind calmodulin (Lu et al, 2015) and could potentially bind light chains such as MYL12.…”

Section: Discussionmentioning

confidence: 99%

“…Not only NM2 but also isoforms such as MYO1C and MYO7A can potentially bind RLC (Morgan et al, 2016; Moreland & Bird, 2022). As a result, the phosphorylation of RLC by MLCK might regulate several aspects of cellular shape and hair-bundle motility.…”

Section: Introductionmentioning

confidence: 99%

Influence of myosin regulatory light chain and myosin light chain kinase on hair cells of the inner ear

Oya,

Woo,

Fabella

et al. 2023

Preprint

View full text Add to dashboard Cite

In the receptor organs of the inner ear and lateral line, sensory hair cells detect mechanical stimuli such as sounds, accelerations, and water movements. In each instance a stimulus deflects the hair bundle, a hair cell's mechanically sensitive organelle. The bundle pivots upon the cell's apical surface, which includes an actin meshwork called the cuticular plate and is surrounded by a ring of filamentous actin and non-muscle myosin II (NM2). Myosin regulatory light chain (RLC) is expressed at the apical surfaces of hair cells and RLC is additionally found in hair bundles. NM2 and the phosphorylation of RLC by myosin light chain kinase (MLCK) have earlier been shown to regulate the sizes and shapes of hair cells' apical surfaces. We have found that inhibitors of NM2 and MLCK reduce the stiffness of hair bundles from the bullfrog's sacculus. Moreover, MLCK inhibition inhibits the spontaneous oscillation of hair bundles and increases the resting open probability of transduction channels. In addition, MLCK inhibition elevates hearing thresholds in mice. We conclude that NM2 and the phosphorylation of RLC modulate slow adaptation and thereby help to set the normal operating conditions of hair bundles.

show abstract

“…It appears that after initiation of stereocilia formation from a patch referred to as microvillus, the Ena/VASP function may be taken over by myosins (myosin IIIA, IIIB, VIIA, and XVA), espin-1, and other proteins (whirlin, harmonin, and Eps8). These proteins are shown to play a key role in bundle length and the maintenance of staircase patterns in stereocilia [ 236 , 243 , 271 , 272 , 273 , 274 , 275 , 276 , 277 ]. However, a recent study suggests that myosin XVA—in its nucleotide-free state—can nucleate actin filaments at the tip of stereocilia, by mediating F-actin inter-subunit contacts [ 278 ].…”

Section: Assembly and Disassembly Of Actin Bundlesmentioning

confidence: 99%

“…Thus, a fine balance between their activity and localization is needed for the maintenance of proper bundle length and shape. The role of myosins in filopodia, microvilli, and stereocilia has been extensively reviewed [ 277 , 310 ].…”

Section: Assembly and Disassembly Of Actin Bundlesmentioning

confidence: 99%

Actin Bundles Dynamics and Architecture

2023

View full text Add to dashboard Cite

Cells use the actin cytoskeleton for many of their functions, including their division, adhesion, mechanosensing, endo- and phagocytosis, migration, and invasion. Actin bundles are the main constituent of actin-rich structures involved in these processes. An ever-increasing number of proteins that crosslink actin into bundles or regulate their morphology is being identified in cells. With recent advances in high-resolution microscopy and imaging techniques, the complex process of bundles formation and the multiple forms of physiological bundles are beginning to be better understood. Here, we review the physiochemical and biological properties of four families of highly conserved and abundant actin-bundling proteins, namely, α-actinin, fimbrin/plastin, fascin, and espin. We describe the similarities and differences between these proteins, their role in the formation of physiological actin bundles, and their properties—both related and unrelated to their bundling abilities. We also review some aspects of the general mechanism of actin bundles formation, which are known from the available information on the activity of the key actin partners involved in this process.

show abstract

Myosin motors in sensory hair bundle assembly

Cited by 13 publications

References 101 publications

Modifications of the endosomal compartment in fibroblasts from sporadic Alzheimer’s disease patients are associated with cognitive impairment

Modifications of the endosomal compartment in fibroblasts from sporadic Alzheimer’s disease patients are associated with cognitive impairment

Influence of myosin regulatory light chain and myosin light chain kinase on hair cells of the inner ear

Actin Bundles Dynamics and Architecture

Contact Info

Product

Resources

About