A Laminin G-EGF-Laminin G Module in Neurexin IV Is Essential for the Apico-Lateral Localization of Contactin and Organization of Septate Junctions

Banerjee, Swati; Paik, Raehum; Mino, Rosa E.; Blauth, Kevin; Fisher, Elizabeth S.; Madden, Victoria J.; Fanning, Alan S.; Bhat, Manzoor A.

doi:10.1371/journal.pone.0025926

Cited by 10 publications

(9 citation statements)

References 44 publications

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“…Subperineurial glia express the cell-adhesion molecule Neurexin IV (NrxIV), a structural component of septate junctions required for the proper establishment of the blood-brain barrier ( Banerjee et al, 2011 ; Banerjee et al, 2006 ; Baumgartner et al, 1996 ; Stork et al, 2008 ). Antibody staining against NrxIV on Flybow clones of ePG4, ePG7 and ePG10 confirms their subperineurial identity ( supplementary material Fig.…”

Section: Resultsmentioning

confidence: 99%

Predetermined embryonic glial cells form the distinct glial sheaths of theDrosophilaperipheral nervous system

et al. 2013

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One of the numerous functions of glial cells in Drosophila is the ensheathment of neurons to isolate them from the potassium-rich haemolymph, thereby establishing the blood-brain barrier. Peripheral nerves of flies are surrounded by three distinct glial cell types. Although all embryonic peripheral glia (ePG) have been identified on a single-cell level, their contribution to the three glial sheaths is not known. We used the Flybow system to label and identify each individual ePG in the living embryo and followed them into third instar larva. We demonstrate that all ePG persist until the end of larval development and some even to adulthood. We uncover the origin of all three glial sheaths and describe the larval differentiation of each peripheral glial cell in detail. Interestingly, just one ePG (ePG2) exhibits mitotic activity during larval stages, giving rise to up to 30 glial cells along a single peripheral nerve tract forming the outermost perineurial layer. The unique mitotic ability of ePG2 and the layer affiliation of additional cells were confirmed by in vivo ablation experiments and layer-specific block of cell cycle progression. The number of cells generated by this glial progenitor and hence the control of perineurial hyperplasia correlate with the length of the abdominal nerves. By contrast, the wrapping and subperineurial glia layers show enormous hypertrophy in response to larval growth. This characterisation of the embryonic origin and development of each glial sheath will facilitate functional studies, as they can now be addressed distinctively and genetically manipulated in the embryo.

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Section: Resultsmentioning

confidence: 99%

Predetermined embryonic glial cells form the distinct glial sheaths of theDrosophilaperipheral nervous system

et al. 2013

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“…For immunoblotting and immunostaining, standard procedures were used (Banerjee et al, 2011). Primary antibodies used were: guinea pig anti-Ringer (1:3000), anti-FasII [Developmental Studies Hybridoma Bank (DSHB), 1:500], anti-ELAV (DSHB, 1:500), anti-Wrap (Wheeler et al, 2009), anti-Slit (DSHB, 1:250), anti-GFP (Life Technologies, 1:500), anti-β-Gal (Promega, 1:500), anti-acetylated-Tubulin (Sigma T7451 and T6793, 1:2000) and anti-α-Tubulin (DSHB, 1:50,000).…”

Section: Ringer Antibody Generation Immunostaining and Immunoblottingmentioning

confidence: 99%

Drosophila Ringmaker regulates microtubule stabilization and axonal extension during embryonic development

Mino

Rogers

Risinger

et al. 2016

Journal of Cell Science

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Axonal growth and targeting are fundamental to the organization of the nervous system, and require active engagement of the cytoskeleton. Polymerization and stabilization of axonal microtubules is central to axonal growth and maturation of neuronal connectivity. Studies have suggested that members of the tubulin polymerization promoting protein (TPPP, also known as P25α) family are involved in cellular process extension. However, no in vivo knockout data exists regarding its role in axonal growth during development. Here, we report the characterization of Ringmaker (Ringer; CG45057), the only Drosophila homolog of long p25α proteins. Immunohistochemical analyses indicate that Ringer expression is dynamically regulated in the embryonic central nervous system (CNS). ringer-null mutants show cell misplacement, and errors in axonal extension and targeting. Ultrastructural examination of ringer mutants revealed defective microtubule morphology and organization. Primary neuronal cultures of ringer mutants exhibit defective axonal extension, and Ringer expression in cells induced microtubule stabilization and bundling into rings. In vitro assays showed that Ringer directly affects tubulin, and promotes microtubule bundling and polymerization. Together, our studies uncover an essential function of Ringer in axonal extension and targeting through proper microtubule organization.

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“…1A). Because CNTNAP2 contains a so-called "neurexin repeat" (LNS-EGF-LNS), it has been suggested that CNTNAPs are members of the neurexin family of synaptic cell adhesion molecules (25,26). CNTN2 consists of six Ig domains followed by four fibronectin domains, and it is tethered to the cell surface by a glycosylphosphatidylinositol anchor (Fig.…”

mentioning

confidence: 99%

Molecular Architecture of Contactin-associated Protein-like 2 (CNTNAP2) and Its Interaction with Contactin 2 (CNTN2)

Reddy

Liu

et al. 2016

Journal of Biological Chemistry

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Contactin-associated protein-like 2 (CNTNAP2) is a large multidomain neuronal adhesion molecule implicated in a number of neurological disorders, including epilepsy, schizophrenia, autism spectrum disorder, intellectual disability, and language delay. We reveal here by electron microscopy that the architecture of CNTNAP2 is composed of a large, medium, and small lobe that flex with respect to each other. Using epitope labeling and fragments, we assign the F58C, L1, and L2 domains to the large lobe, the FBG and L3 domains to the middle lobe, and the L4 domain to the small lobe of the CNTNAP2 molecular envelope. Our data reveal that CNTNAP2 has a very different architecture compared with neurexin 1␣, a fellow member of the neurexin superfamily and a prototype, suggesting that CNTNAP2 uses a different strategy to integrate into the synaptic protein network. We show that the ectodomains of CNTNAP2 and contactin 2 (CNTN2) bind directly and specifically, with low nanomolar affinity. We show further that mutations in CNTNAP2 implicated in autism spectrum disorder are not segregated but are distributed over the whole ectodomain. The molecular shape and dimensions of CNTNAP2 place constraints on how CNTNAP2 integrates in the cleft of axo-glial and neuronal contact sites and how it functions as an organizing and adhesive molecule.

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A Laminin G-EGF-Laminin G Module in Neurexin IV Is Essential for the Apico-Lateral Localization of Contactin and Organization of Septate Junctions

Cited by 10 publications

References 44 publications

Predetermined embryonic glial cells form the distinct glial sheaths of theDrosophilaperipheral nervous system

Predetermined embryonic glial cells form the distinct glial sheaths of theDrosophilaperipheral nervous system

Drosophila Ringmaker regulates microtubule stabilization and axonal extension during embryonic development

Molecular Architecture of Contactin-associated Protein-like 2 (CNTNAP2) and Its Interaction with Contactin 2 (CNTN2)

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