The Dynamic and Complex Role of the Joubert Syndrome-Associated Ciliary Protein, ADP-Ribosylation Factor-Like GTPase 13B (ARL13B) in Photoreceptor Development and Maintenance

Dilan, Tanya L.; Ramamurthy, Visvanathan

doi:10.1007/978-3-030-27378-1_82

Cited by 3 publications

(7 citation statements)

References 25 publications

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“…[46][47][48][49][50][51]163,[171][172][173][174][175][176] Among one of the ARF GTPases LM markers, the arl13b label revealed comforted this signaling process expressed as one of its characteristic proteins doting those microtubule-associated out of the centrioles, [45][46][47][48][49][50][51][52][53] and mutated in Joubert syndrome and other ciliopathies. 177,178 The immunolabel arl13b well characterized a primary cilium, transient to be along a cell cycle mitosis but resuming into oligodendrocyte extension elongation and remyelination [45][46][47][48][49][50][51] as illustrated in Figure 8A.…”

Section: C3 the Oligodendrocyte Primary Ciliummentioning

confidence: 94%

“…Hedgehog (Hh) signal transduction pathway in mice (as well as other mammals) is favorable to and necessary for the development and patterning the intracellular transport of vesicles sorted from the Golgi apparatus [as reported in the previous paragraph with arl13b protein revelation [45][46][47][48][49][50][51][52][53][172][173][174][175][176][177][178][179][180][181][182] and effecting the homeostatic turnover of 'used' molecular entities with autophagocytosis, using the endosome as shown later, as enlarged (in ODS48h of Fig 13 C), collecting as lipofuscin bodies. This cell's vesicles were shown in numbers contained in these ODS12h oligodendrocytes along with the primary cilium have been called by a misnomer 'intraflagellar' transport (IFT)' -even though there is no 'flagellum' builtduring this intracellular built up!…”

Section: C4 Intracellular Vesicles: Resolution Of Transcriptional and Translational Activitiesmentioning

confidence: 99%

“…This cell's vesicles were shown in numbers contained in these ODS12h oligodendrocytes along with the primary cilium have been called by a misnomer 'intraflagellar' transport (IFT)' -even though there is no 'flagellum' builtduring this intracellular built up! We use 'IFT' here only to acknowledge previous important studies of these Golgi secretory intracellular transports of peculiar phospholipids [172][173][174][175][176][177][178][179][180][181][182][183][184][185][186][187][188][189][190] with a terminology that should be amended as 'cilum-associated vesicles' (CAV) to encompass those that are being built and those that contained recycled components. These intracellular CAV vesicles cannot be dispatched to the plasmalemma surface because either the restrained space caused by crowding of the neuropil and neighboring macroglia and nerve cell bodies for a final outwardly exhibition or because the 'program' for building has been arrested due to reestablishment of differentiation, as seen at the 36-hour stage afterward.…”

Section: C4 Intracellular Vesicles: Resolution Of Transcriptional and Translational Activitiesmentioning

confidence: 99%

“…Primary cilia are highly conserved multifunctional cell organelles that extend from the cell membrane, there, a wide range of genetic disorders, collectively termed ciliopathies, is attributed to primary cilia dysfunction, such as the Joubert syndrome. 175,178 Another archetypical ciliopathy is the Bardet-Biedl syndrome (BBS) where patients displayed all symptoms associated with dysfunctional cilia as in several other ciliopathies. One can see that the primary cilium acts as a sensory organelle transmitting intra-and extracellular signals as well as transfer phospholipids thereby transducing various signaling pathways facilitated by the BBS proteins.…”

Section: C5 the Oligodendrocyte Primary Cilium Is Labeled With Arl13b Antibodymentioning

confidence: 99%

“…One can see that the primary cilium acts as a sensory organelle transmitting intra-and extracellular signals as well as transfer phospholipids thereby transducing various signaling pathways facilitated by the BBS proteins. 178 Other growing evidences suggest that cilia proteins also have alternative functions in ciliary independent mechanisms, which might be contributing to disease etiology such as the family of ARF G proteins associated with the regulations of ATPases involved in the intracellular transport, [42][43][44][45][46][47][48][49][50][171][172][173] including that of ciliogenesis (i.e., basal bodies and microtubule built up. [180][181][182][183][184][185][186] Thus, label for arl13b was strongly labeled at ODS12h specifically along with the detection of a polar particle-like that expanded with elongation, adjacent to the satellite oligodendrocytes by further encompassing the growth cone out of the cell bodies.…”

Section: C5 the Oligodendrocyte Primary Cilium Is Labeled With Arl13b Antibodymentioning

confidence: 99%

See 4 more Smart Citations

A primary cilium in oligodendrocytes: a fine structure signal of repairs in thalamic Osmotic Demyelination Syndrome (ODS)

Gilloteaux

Bouchat

Bielarz

et al. 2021

Ultrastructural Pathology

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A murine osmotic demyelination syndrome (ODS) model of the central nervous system included the relay thalamic ventral posterolateral (VPL) and ventral posteromedial (VPM) nuclei. Morphologic comparisons between treatments have revealed oligodendrocyte changes and, already 12 hours following the osmolality restoration, some heavily contrasted oligodendrocytes formed a unique intracellular primary cilium. This unique structure, found in vivo, in mature CNS oligodendrocytes, could account for a local awakening of some of the developmental proteome as it can be expressed in oligodendrocyte precursor cells. This resilience accompanied the emergence of arl13b protein expression along with restoration of nerve cell body axon hillocks shown in a previous issue of this journal. Additionally, the return of several thalamic oligodendrocyte fine features (nucleus, organelles) was shown 36 h later, including some mitosis. Those cell restorations and recognized translational activities comforted that local repairs could again take place, due to oligodendrocyte resilience after ODS instead or added to a postulated immigration of oligodendrocyte precursor cells distant from the sites of myelinolysis.

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Section: C3 the Oligodendrocyte Primary Ciliummentioning

confidence: 94%

Section: C4 Intracellular Vesicles: Resolution Of Transcriptional and Translational Activitiesmentioning

confidence: 99%

Section: C4 Intracellular Vesicles: Resolution Of Transcriptional and Translational Activitiesmentioning

confidence: 99%

Section: C5 the Oligodendrocyte Primary Cilium Is Labeled With Arl13b Antibodymentioning

confidence: 99%

Section: C5 the Oligodendrocyte Primary Cilium Is Labeled With Arl13b Antibodymentioning

confidence: 99%

See 3 more Smart Citations

A primary cilium in oligodendrocytes: a fine structure signal of repairs in thalamic Osmotic Demyelination Syndrome (ODS)

Gilloteaux

Bouchat

Bielarz

et al. 2021

Ultrastructural Pathology

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ARF family GTPases with links to cilia

Fisher

Kuna

Caspary

et al. 2020

American Journal of Physiology-Cell Physiology

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The ARF superfamily of regulatory GTPases, including both the ARF and ARL proteins, control a multitude of cellular functions including aspects of vesicular traffic, lipid metabolism, mitochondrial architecture, the assembly and dynamics of the microtubule and actin cytoskeletons, and other pathways in cell biology. Considering their general utility, it is perhaps not surprising that increasingly ARF/ARLs have been found in connection to primary cilia. Here, we critically evaluate the current knowledge of the role four ARF/ARLs (ARF4, ARL3, ARL13B and ARL6) play in cilia and highlight key missing information that would help move our understanding forward. Importantly, these GTPases are themselves regulated by guanine nucleotide exchange factors (GEFs) that activate them and by GTPase activating proteins (GAPs) that act as both effectors and terminators of signaling. We believe that the identification of the GEFs and GAPs and better models of the actions of these GTPases and their regulators will provide a much deeper understanding and appreciation of the mechanisms that underly ciliary functions and the causes of a number of human ciliopathies.

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AUY922 induces retinal toxicity through attenuating TRPM1

et al. 2021

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Background Ocular adverse events are common dose-limiting toxicities in cancer patients treated with HSP90 inhibitors, such as AUY922; however, the pathology and molecular mechanisms that mediate AUY922-induced retinal toxicity remain undescribed. Methods The impact of AUY922 on mouse retinas and cell lines was comprehensively investigated using isobaric tags for relative and absolute quantitation (iTRAQ)‑based proteomic profiling and pathway enrichment analysis, immunohistochemistry and immunofluorescence staining, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, MTT assay, colony formation assay, and western blot analysis. The effect of AUY922 on the Transient Receptor Potential cation channel subfamily M member 1 (TRPM1)-HSP90 chaperone complex was characterized by coimmunoprecipitation. TRPM1-regulated gene expression was analyzed by RNAseq analysis and gene set enrichment analysis (GSEA). The role of TRPM1 was assessed using both loss-of-function and gain-of-function approaches. Results Here, we show that the treatment with AUY922 induced retinal damage and cell apoptosis, dysregulated the photoreceptor and retinal pigment epithelium (RPE) layers, and reduced TRPM1 expression. Proteomic profiling and functional annotation of differentially expressed proteins reveals that those related to stress responses, protein folding processes, regulation of apoptosis, cell cycle and growth, reactive oxygen species (ROS) response, cell junction assembly and adhesion regulation, and proton transmembrane transport were significantly enriched in AUY922-treated cells. We found that AUY922 triggered caspase-3-dependent cell apoptosis, increased ROS production and inhibited cell growth. We determined that TRPM1 is a bona fide HSP90 client and characterized that AUY922 may reduce TRPM1 expression by disrupting the CDC37-HSP90 chaperone complex. Additionally, GSEA revealed that TRPM1-regulated genes were associated with retinal morphogenesis in camera-type eyes and the JAK-STAT cascade. Finally, gain-of-function and loss-of-function analyses validated the finding that TRPM1 mediated the cell apoptosis, ROS production and growth inhibition induced by AUY922. Conclusions Our study demonstrates the pathology of AUY922-induced retinal toxicity in vivo. TRPM1 is an HSP90 client, regulates photoreceptor morphology and function, and mediates AUY922-induced cytotoxicity.

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The Dynamic and Complex Role of the Joubert Syndrome-Associated Ciliary Protein, ADP-Ribosylation Factor-Like GTPase 13B (ARL13B) in Photoreceptor Development and Maintenance

Cited by 3 publications

References 25 publications

A primary cilium in oligodendrocytes: a fine structure signal of repairs in thalamic Osmotic Demyelination Syndrome (ODS)

A primary cilium in oligodendrocytes: a fine structure signal of repairs in thalamic Osmotic Demyelination Syndrome (ODS)

ARF family GTPases with links to cilia

AUY922 induces retinal toxicity through attenuating TRPM1

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