A5038596476- Retinal Development and Disorders
- Photoreceptor and optogenetics research
- Cellular transport and secretion
- Microtubule and mitosis dynamics
- Retinal Diseases and Treatments
- Receptor Mechanisms and Signaling
- Genetic and Kidney Cyst Diseases
- Ubiquitin and proteasome pathways
- Cell Adhesion Molecules Research
- Connective tissue disorders research
- Protist diversity and phylogeny
- Mitochondrial Function and Pathology
- Neuroscience and Neuropharmacology Research
- Ion channel regulation and function
- Axon Guidance and Neuronal Signaling
- Neuroinflammation and Neurodegeneration Mechanisms
- Hedgehog Signaling Pathway Studies
- Nerve injury and regeneration
- Renal and related cancers
- Photochromic and Fluorescence Chemistry
- ATP Synthase and ATPases Research
- Wnt/β-catenin signaling in development and cancer
- Retinal and Macular Surgery
- Caveolin-1 and cellular processes
- Hippo pathway signaling and YAP/TAZ
Cornell University
2014-2024
Weill Cornell Medicine
2018-2024
Ophthalmology Associates (United States)
2019
New York Proton Center
2015
Zero to Three
2006
Dyson (United Kingdom)
1999-2001
New York University
2001
Singapore Eye Research Institute
1999
The interaction of cytoplasmic dynein with its cargoes is thought to be indirectly mediated by dynactin, a complex that binds the intermediate chain. However, roles other subunits in cargo binding have been unknown. Here we demonstrate translocates rhodopsin-bearing vesicles along microtubules. This occurs directly between C-terminal tail rhodopsin and Tctex-1, light mutations responsible for retinitis pigmentosa inhibit this interaction. Our results point an alternative docking mechanism...
The innate immune system relies on evolutionally conserved Toll-like receptors (TLRs) to recognize diverse microbial molecular structures. Most TLRs depend a family of adaptor proteins termed MyD88s transduce their signals. Critical roles MyD88-1-4 in host defense were demonstrated by defective responses knockout mice. In contrast, the sites expression and functions vertebrate MyD88-5 have remained elusive. We show that is distinct from other preferentially expressed neurons, colocalizes...
Nerve growth factor (NGF) initiates its trophic effects by longrange signaling through binding, internalization, and transport of a ligand-receptor complex from the axon terminal to cell body.However, mechanism which retrograde NGF takes place has not been elucidated.Here we describe an interaction between Trk receptor tyrosine kinase 14 kDa light chain cytoplasmic dynein.After transfection in human embryonic kidney 293 cells, this dynein was found bind TrkA, TrkB, TrkC receptors.Mapping...
All basolateral sorting signals described to date reside in the cytoplasmic domain of proteins, whereas apical targeting motifs have been found be lumenal. In this report, we demonstrate that wild-type rhodopsin is targeted plasma membrane via TGN upon expression polarized epithelial MDCK cells. Truncated with a deletion 32 COOH-terminal residues shows nonpolar steady-state distribution. Addition 39 redirects protein CD7 membrane. Fusion rhodopsin's tail cytosolic glutathione S-transferase...
Emerging data suggest that in polarized epithelial cells newly synthesized apical and basolateral plasma membrane proteins traffic through different endosomal compartments en route to the respective cell surface. However, direct evidence for trans-endosomal pathways of is still missing mechanisms involved are poorly understood. Here, we imaged entire biosynthetic rhodopsin-GFP, an marker cells, synchronized recombinant conditional aggregation domains, live Madin-Darby canine kidney using...
Abstract Age-related macular degeneration (AMD) is the leading cause of blindness among elderly. Dry AMD has unclear etiology and no treatment. Lipid-rich drusen are hallmark dry AMD. An mouse model insights into drusenogenesis keys to better understanding this disease. Chloride intracellular channel 4 (CLIC4) a pleomorphic protein regulating diverse biological functions. Here we show that retinal pigment epithelium (RPE)-specific Clic4 knockout mice exhibit full spectrum functional...
Oxidative stress has been implicated in the pathogenesis of age-related macular degeneration, leading cause blindness older adults, with retinal pigment epithelium (RPE) cells playing a key role. To better understand cytotoxic mechanisms underlying oxidative stress, we used cell culture and mouse models iron overload, as can catalyze reactive oxygen species formation RPE. Iron-loading cultured induced pluripotent stem cell-derived RPE increased lysosomal abundance, impaired proteolysis...
Molecular chaperones are involved in a wide range of cellular events, such as protein folding and oligomeric complex assembly. DnaK- DnaJ-like proteins the two major classes molecular mammals. Recent studies have shown that family can inhibit polyglutamine aggregation, hallmark many neurodegenerative diseases, including Huntington's disease (HD). Although most studied ubiquitously expressed, some restricted expression, so it is possible specific may affect aggregation neurons. In this...
A novel class of intracellular chloride channels, the p64 family, has been found on several types vesicles. These acting in concert with electrogenic proton pump, regulate pH vesicle interior, which is critical for vesicular function. Here we describe molecular cloning p64H1, a homolog, from both human and cow. Northern blot analysis showed that p64H1 expressed abundantly brain retina, whereas other members this family (e.g., NCC27) are only at low levels these tissues. Immunohistochemical...
Retinitis pigmentosa (RP) is a clinically and genetically heterogeneous degenerative eye disease. Mutations at Arg135 of rhodopsin are associated with severe form autosomal dominant RP. This report presents evidence that mutant rhodopsins (e.g., R135L, R135G, R135W) hyperphosphorylated bind high affinity to visual arrestin. Mutant recruits the cytosolic arrestin plasma membrane, rhodopsin-arrestin complex internalized into endocytic pathway. Furthermore, complexes alter morphology endosomal...
Rab5, a member of the small GTPase family proteins, is primarily localized on early endosomes and has been proposed to participate in regulation endosome trafficking. It reported that phosphatidylinositol 3-kinases FYVE domain such as EEA1, can be recruited onto act Rab5 effectors. SARA (Smad anchor for receptor activation), also protein, was initially isolated participant signal transduction from transforming growth factor beta receptor. Overexpressed found EEA1-positive endosomes. In this...
Cilia are vital to various cellular and sensory functions. The pathway by which ciliary membrane proteins translocate through the transition zone is not well understood. Direct morphological characterization of cargoes in transit remains lacking. In vertebrate photoreceptor, rhodopsin synthesized transported from inner segment disc membranes outer (OS), a modified cilium. To date, topology basal OS mechanisms (i.e., connecting cilium) nascent formed remain controversial. Using an antibody...
Retinal detachment is a sight-threatening condition. The molecular mechanism underlying the adhesion between RPE and photoreceptors poorly understood because intimate interactions these two cell types are impossible to model study in vitro. In this article, we show that chloride intracellular channel 4 (CLIC4) enriched at apical microvilli, which interdigitated with photoreceptor outer segment. We used novel plasmid-based transfection method cell-autonomously suppress CLIC4 situ. silenced...
Highlights•Light regulates the rod OS entry of rhodopsin•PRPH2 enters following a rhythm complementary to that rhodopsin•Rod discs formed during day and night have distinct composition morphology•Cyclic light governs periodicity disc arrangement cytostructureSummaryThe outer segment (OS) photoreceptor is light-sensing cilium containing ∼1,000 membrane-bound discs. Each day, constituting distal tenth are shed, whereas nascent at base through incorporation molecules transported from inner...
Abstract Vacuolar protein sorting 35 (VPS35), the core component of retromer complex which regulates endosomal trafficking, is genetically linked with Parkinson’s disease (PD). Impaired vision a common non-motor manifestation PD. Here, we show mouse retinas VPS35-deficient rods exhibit synapse loss and visual deficit, followed by progressive degeneration concomitant emergence Lewy body-like inclusions phospho-α-synuclein (P-αSyn) aggregation. Ultrastructural analyses reveal accumulate...
Peripherin 2 (PRPH2) is a tetraspanin protein concentrated in the light-sensing cilium (called outer segment) of vertebrate photoreceptor. The mechanism underlying ciliary targeting PRPH2 and etiology cone dystrophy caused by mutations remain elusive. Here we show that late endosome (LE) main waystation critically sorts newly synthesized to cilium. expressed luminal membrane LE. We delineate multiple C-terminal motifs distinctively regulate its LE through ubiquitination binding ESCRT...
Cytoplasmic dynein is a multi-subunit protein complex in which each subunit encoded by few genes. How these isoforms are assembled and regulated to mediate the diverse functions of cytoplasmic unknown. We previously have shown that two highly conserved 14 kDa light chains, Tctex-1 RP3, different cargo-binding abilities. In this report, coimmunoprecipitation revealed RP3 were present mutually exclusive complexes brain. Two specific antibodies used examine localization chains adult rat...
Abstract Dysregulation in the extracellular matrix (ECM) microenvironment surrounding retinal pigment epithelium (RPE) has been implicated etiology of proliferative vitreoretinopathy and age-related macular degeneration. The regulation ECM remodeling by RPE cells is not well understood. We show that membrane-type metalloproteinase 14 (MMP14) central to degradation at focal adhesions human ARPE19 cells. degradative activity, but assembly, adhesion regulated chloride intracellular channel 4...
Dynein light chains are accessory subunits of the cytoplasmic dynein complex, a minus-end directed microtubule motor. Here, we demonstrate that chain Tctex-1 associates with unattached kinetochores and is essential for accurate chromosome segregation. knockdown in cells does not affect localization function at kinetochore, but produces prolonged mitotic arrest few misaligned chromosomes, which subsequently missegregated during anaphase. This independent Tctex-1's association dynein. The...