Harnessing molecular motors for nanoscale pulldown in live cells

Bird, Jonathan E.; Barzik, Melanie; Drummond, Meghan C.; Sutton, Daniel C.; Goodman, Spencer; Morozko, Eva L.; Cole, Stacey M.; Boukhvalova, Alexandra; Skidmore, Jennifer; Syam, Diana; Wilson, Elizabeth A.; Fitzgerald, Tracy S.; Rehman, Atteeq U.; Martin, Donna M.; Boger, Erich T.; Belyantseva, Inna A.; Friedman, Thomas B.

doi:10.1091/mbc.e16-08-0583

Cited by 26 publications

(44 citation statements)

References 70 publications

(70 reference statements)

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“…The images were converted to tagged image file format (TIFF). Filopodia were then selected and signals at their tips quantified using the FIJI-based procedure and MATLAB software described by Bird and colleagues (NanoSPD [48]). 33 cells representing 3 independent experiments were selected for each condition, and 126 (MYC) versus 225 (MYC:GPSM2) filopodia that passed the selection process were analyzed.…”

Section: Immunofluorescence Image Analysismentioning

confidence: 99%

GPSM2-GNAI Specifies the Tallest Stereocilia and Defines Hair Bundle Row Identity

et al. 2019

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GPSM2-GNAI Specifies the Tallest Stereocilia and Defines Hair Bundle Row Identity Highlights d GPSM2, GNAI, WHRN, MYO15A, and EPS8 work in the same pathway to shape hair bundles d GPSM2-GNAI-WHRN is a late module added to MYO15A-EPS8 at row 1 stereocilia tips only d GPSM2-GNAI defines the identity of the tallest, first-row stereocilia d Mutant bundles comprise generic stereocilia lacking differential row identity

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Section: Immunofluorescence Image Analysismentioning

confidence: 99%

GPSM2-GNAI Specifies the Tallest Stereocilia and Defines Hair Bundle Row Identity

et al. 2019

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“…Eventually, Chd7 expression becomes enriched in specific cells and tissues, especially in organs where malformations are known to occur in CHARGE. CHD7 is localized primarily to the nucleus, although a recent study suggested it may also localize to inner ear stereocilia [Bird et al, 2017]. Chd7 expression in mouse neural tissues likely reflects its important functions in a wide variety of peripheral and central nervous system regions.…”

Section: Chd7 Gene Structure Expression Evolutionary Conservation mentioning

confidence: 99%

Inner ear manifestations in CHARGE: Abnormalities, treatments, animal models, and progress toward treatments in auditory and vestibular structures

Choo

Tawfik

Martin

et al. 2017

American J of Med Genetics Pt C

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The inner ear contains the sensory organs for hearing and balance. Both hearing and balance are commonly affected in individuals with CHARGE syndrome (CS), an autosomal dominant condition caused by heterozygous pathogenic variants in the CHD7 gene. Semicircular canal dysplasia or aplasia is the single most prevalent feature in individuals with CHARGE leading to deficient gross motor skills and ambulation. Identification of CHD7 as the major gene affected in CHARGE has enabled acceleration of research in this field. Great progress has been made in understanding the role of CHD7 in the development and function of the inner ear, as well as in related organs such as the middle ear and auditory and vestibular neural pathways. The goals of current research on CHD7 and CS are to (a) improve our understanding of the pathology caused by CHD7 pathogenic variants and (b) to provide better tools for prognosis and treatment. Current studies utilize cells and whole animals, from flies to mammals. The mouse is an excellent model for exploring mechanisms of Chd7 function in the ear, given the evolutionary conservation of ear structure, function, Chd7 expression, and similarity of mutant phenotypes between mice and humans. Newly recognized developmental functions for mouse Chd7 are shedding light on how abnormalities in CHD7 might lead to CS symptoms in humans. Here we review known human inner ear phenotypes associated with CHD7 pathogenic variants and CS, summarize progress toward diagnosis and treatment of inner ear-related pathologies, and explore new avenues for treatment based on basic science discoveries.

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“…To further explore the molecular mechanism of CIB2-mediated mTORC1 modulation, we assessed direct interactions between CIB2 and TSC1, TSC2, mTORC1-specifc subunit Raptor, mTOR kinase, and Rheb, using a previously reported nanoscale pulldown 2.0 (NanoSPD) quantitative interaction assay 32 . NanoSPD utilizes a construct (nanoTRAP) consisting of GFP nanobody fused with the heavy meromyosin (HMM domain) of myosin 10 (myo10 HMM -GFP nanobody).…”

Section: Cib2 Forms a Tripartite Complex With Raptor-mtormentioning

confidence: 99%

CIB2 regulates autophagy via Rheb-mTORC1 signaling axis

Sethna

Bernstein

Jian

et al. 2020

Preprint

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SUMMARYAge-related macular degeneration (AMD), a multifactorial neurodegenerative disorder, is the most common cause of vision loss in the elderly. Deficits in autophagy have been associated with age-related retinal pigment epithelium (RPE) pathology in mice, and dry-AMD in humans. In this study, we establish that the calcium and integrin binding protein 2 (CIB2) regulates autophagy in the RPE via Rheb-mTORC1 signaling axis. Cib2 mutant mice have reduced autophagic clearance in RPE and increased mTORC1 signaling – a negative regulator of autophagy. Concordant molecular deficits were also observed in RPE/choroid tissues from humans affected with dry AMD. Mechanistically, CIB2 negatively regulates mTORC1 by preferentially binding to ‘nucleotide empty’ or inactive GDP-loaded Rheb. Upregulated mTORC1 signaling has been implicated in aging, Tuberous sclerosis complex (TSC), and lymphangioleiomyomatosis (LAM) cancer. Over-expressing CIB2 in LAM patient-derived fibroblasts and Tsc2 null cell line down-regulates hyperactive mTORC1 signaling. Thus, our findings have significant ramifications for the etiology of AMD and mTORC1 hyperactivity disorders and treatments.

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Harnessing molecular motors for nanoscale pulldown in live cells

Cited by 26 publications

References 70 publications

GPSM2-GNAI Specifies the Tallest Stereocilia and Defines Hair Bundle Row Identity

GPSM2-GNAI Specifies the Tallest Stereocilia and Defines Hair Bundle Row Identity

Inner ear manifestations in CHARGE: Abnormalities, treatments, animal models, and progress toward treatments in auditory and vestibular structures

CIB2 regulates autophagy via Rheb-mTORC1 signaling axis

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