A Conserved Role for Girdin in Basal Body Positioning and Ciliogenesis

Nechipurenko, Inna V.; Olivier-Mason, Anique; Kazatskaya, Anna; Kennedy, Julie; McLachlan, Ian G.; Heiman, Maxwell G.; Blacque, Oliver E.; Sengupta, Piali

doi:10.1016/j.devcel.2016.07.013

Cited by 51 publications

(68 citation statements)

References 53 publications

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“…However, the amphid neurons AWA and AWB exhibited weaklypenetrant dendrite extension defects in grdn-1 (Figs. 4, S5), consistent with a previous report that noted aberrant branching and other morphological defects (Nechipurenko et al, 2016). These defects could reflect a primary role for GRDN-1 during AWA and AWB dendrite extension, or could be secondary to defects in basal body positioning in these neurons, as many mutants that disrupt the ciliary basal body or transition zone also produce some amphid dendrite defects (CHE-10, Fig.…”

Section: Sax-7 and Grdn-1 Are Not Broadly Required For Dendrite Extensupporting

confidence: 89%

“…S8B). These puncta were previously shown to localize to the basal bodies at the ciliated endings of sensory dendrites (Nechipurenko et al, 2016). However, as glia are not ciliated, we were curious how GRDN-1 would localize in these cells.…”

Section: Grdn-1 Localizes In Glia To Puncta Near Dendrite Contactsmentioning

confidence: 90%

“…In summary, it is intriguing that our screen exclusively identified alleles of sax-7 and grdn-1, and that similar phenotypes are not caused by mutations in known factors that interact with SAX-7 and GRDN-1 during neuronal development. However, in addition to their roles in neurons, SAX-7 and GRDN-1 are also expressed broadly in epithelial tissues during embryonic development (Chen et al, 2001;Nechipurenko et al, 2016). An interesting possibility is that factors that interact with them during epithelial development might promote URX and BAG dendrite extension but were not identified in our screens due to other, essential roles.…”

Section: Grdn-1mentioning

confidence: 92%

“…These results suggest that, although they require the same factors for dendrite extension, URX and BAG are likely to exhibit some developmental differences. Importantly, a grdn-1 deletion allele (tm6493) causes completely penetrant embryonic lethality (Nechipurenko et al, 2016), suggesting this gene plays an essential role in early development. This leads to three inferences.…”

Section: Grdn-1mentioning

confidence: 99%

“…SAX-7 is expressed broadly in epithelia, localizes to epithelial cell junctions, and can act redundantly with the classical epithelial cell junction protein HMR-1/cadherin during early development (Chen et al, 2001;Grana et al, 2010). GRDN-1 is partly required for localization of the epithelial cell junction marker AJM-1 and, in Drosophila, Girdin localizes to epithelial adherens junctions, physically interacts with the cadherin-catenin complex protein α-catenin, and is required to maintain epithelial cell adhesion during large-scale morphogenetic movements (Ha et al, 2015;Houssin et al, 2015;Nechipurenko et al, 2016).…”

Section: Possible Molecular Mechanisms For Sax-7 and Grdn-1mentioning

confidence: 99%

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Dendrites with specialized glial attachments develop by retrograde extension using SAX-7 and GRDN-1

Cebul

McLachlan

Heiman

2019

Preprint

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Dendrites develop elaborate morphologies in concert with surrounding glia, but the molecules that coordinate dendrite and glial morphogenesis are mostly unknown. C. elegans offers a powerful model for identifying such factors. Previous work in this system examined dendrites and glia that develop within epithelia, similar to mammalian sense organs. Here, we focus on the neurons BAG and URX, which are not part of an epithelium but instead form membranous attachments to a single glial cell at the nose, reminiscent of dendrite-glia contacts in the mammalian brain. We show that these dendrites develop by retrograde extension, in which the nascent dendrite endings anchor to the presumptive nose and then extend by stretch during embryo elongation. Using forward genetic screens, we find that dendrite development requires the adhesion protein SAX-7/L1CAM and the cytoplasmic protein GRDN-1/CCDC88C to anchor dendrite endings at the nose. SAX-7 acts in neurons and glia, while GRDN-1 acts in glia to nonautonomously promote dendrite extension. Thus, this work shows how glial factors can help to shape dendrites, and identifies a novel molecular mechanism for dendrite growth by retrograde extension.C. elegans offers several advantages. Each cell can be uniquely identified and has a remarkably stereotyped shape and set of cell-cell contacts; neuron-and glia-specific promoters allow the targeted expression of transgenes in single cells to visualize and manipulate specific neuron-glia contacts in intact living animals; and its powerful genetics permit unbiased screens to identify factors that control neuron-glia interactions. Additionally, C. elegans glia share a number of important features with mammalian glia (Mizeracka and Heiman, 2015). This system Retrograde extension by SAX-7 and GRDN-1 4 thus offers a powerful genetic model for dissecting dendrite-glia contacts. Here, we turned our attention to a previously overlooked class of dendrite-glia contacts whose elaborate, tightly apposed membranous structures are reminiscent of the highly coordinated membranous contacts found between astrocytes and dendritic spines at mammalian synapses.Using super-resolution microscopy, we find that the dendrites of two neuron types, URX and BAG, form specialized attachments with a single glial partner. Using forward genetics, we identify two conserved molecules, SAX-7 and GRDN-1, that are required for the development of these dendrites. SAX-7 is a homolog of the mammalian neuron-glia adhesion molecule L1CAM, and GRDN-1 is a homolog of proteins involved in cell polarity and cytoskeleton organization.Each of these homologs is expressed in the mammalian brain and causes developmental brain disorders when disrupted (Jouet et al., 1994;Vits et al., 1994; Ekici et al., 2010). Using embryonic time-course imaging, we find that URX and BAG dendrites develop by retrograde extension, a type of outgrowth in which the dendrites anchor to their targets and then extend by stretch. SAX-7 and GRDN-1 help to anchor dendrite endings at the nose during embryo elong...

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Section: Sax-7 and Grdn-1 Are Not Broadly Required For Dendrite Extensupporting

confidence: 89%

Section: Grdn-1 Localizes In Glia To Puncta Near Dendrite Contactsmentioning

confidence: 90%

Section: Grdn-1mentioning

confidence: 92%

Section: Grdn-1mentioning

confidence: 99%

Section: Possible Molecular Mechanisms For Sax-7 and Grdn-1mentioning

confidence: 99%

See 3 more Smart Citations

Dendrites with specialized glial attachments develop by retrograde extension using SAX-7 and GRDN-1

Cebul

McLachlan

Heiman

2019

Preprint

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Chronically activated microglia in ALS gradually lose their immune functions and develop unconventional proteome

Barreto‐Núñez,

Béland,

Boutej

et al. 2024

Glia

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Neuroinflammation and chronic activation of microglial cells are the prominent features of amyotrophic lateral sclerosis (ALS) pathology. While alterations in the mRNA profile of diseased microglia have been well documented, the actual microglia proteome remains poorly characterized. Here we performed a functional characterization together with proteome analyses of microglial cells at different stages of disease in the SOD1‐G93A model of ALS. Functional analyses of microglia derived from the lumbar spinal cord of symptomatic mice revealed: (i) remarkably high mitotic index (close to 100% cells are Ki67+) (ii) significant decrease in phagocytic capacity when compared to age‐matched control microglia, and (iii) diminished response to innate immune challenges in vitro and in vivo. Proteome analysis revealed a development of two distinct molecular signatures at early and advanced stages of disease. While at early stages of disease, we identified several proteins implicated in microglia immune functions such as GPNMB, HMBOX1, at advanced stages of disease microglia signature at protein level was characterized with a robust upregulation of several unconventional proteins including rootletin, major vaults proteins and STK38. Upregulation of GPNMB and rootletin has been also found in the spinal cord samples of sporadic ALS. Remarkably, the top biological functions of microglia, in particular in the advanced disease, were not related to immunity/immune response, but were highly enriched in terms linked to RNA metabolism. Together, our results suggest that, over the course of disease, chronically activated microglia develop unconventional protein signatures and gradually lose their immune identity ultimately turning into functionally inefficient immune cells.

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Psychiatric behaviors associated with cytoskeletal defects in radial neuronal migration

Fukuda

Yanagi

2017

Cell. Mol. Life Sci.

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Normal development of the cerebral cortex is an important process for higher brain functions, such as language, and cognitive and social functions. Psychiatric disorders, such as schizophrenia and autism, are thought to develop owing to various dysfunctions occurring during the development of the cerebral cortex. Radial neuronal migration in the embryonic cerebral cortex is a complex process, which is achieved by strict control of cytoskeletal dynamics, and impairments in this process are suggested to cause various psychiatric disorders. Our recent findings indicate that radial neuronal migration as well as psychiatric behaviors is rescued by controlling microtubule stability during the embryonic stage. In this review, we outline the relationship between psychiatric disorders, such as schizophrenia and autism, and radial neuronal migration in the cerebral cortex by focusing on the cytoskeleton and centrosomes. New treatment strategies for psychiatric disorders will be discussed.

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A Conserved Role for Girdin in Basal Body Positioning and Ciliogenesis

Cited by 51 publications

References 53 publications

Dendrites with specialized glial attachments develop by retrograde extension using SAX-7 and GRDN-1

Dendrites with specialized glial attachments develop by retrograde extension using SAX-7 and GRDN-1

Chronically activated microglia in ALS gradually lose their immune functions and develop unconventional proteome

Psychiatric behaviors associated with cytoskeletal defects in radial neuronal migration

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