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Deciphering the function of neurexins at cellular junctions.

Littleton JT, Bhat MA, Bellen HJ - J. Cell Biol. (1997)

View Article: PubMed Central - PubMed

Affiliation: Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas 77030, USA.

ABSTRACT

Recent in vitro and in vivo studies have provided exciting insights suggesting that the neurexin family may function in organizing cellular junctions. This model is supported by the phenotypic analysis of Drosophila neurexin mutations (2). These mutants lack the ladder-like transcellular septate characteristic of septate junctions. In addition, neurexin is required in glia to form the blood–brain barrier, consistent with an ability of neurexins to form transcellular barriers at cellular junctions. Neurexin also localizes protein 4.1 to sites of cell contact, and neurexin mutations show defects in dorsal closure of the epidermis, a process requiring extensive cellular movements and signaling. Fig. 2 presents a model of a cellular junction incorporating neurexins.

Essential questions remain to be answered concerning the neurexins. Foremost, a precise subcellular location of the known vertebrate neurexins is required to determine if they may also be involved in axonal–glial interactions, similar to that reported for the NRX IV homologue, hNRX IV/Caspr. In addition, it will be important to extend the search for nonneuronal neurexins, as a more complete catalog of the neurexin family is required to begin to determine the variety of roles these proteins might play in cellular junctions. Do neurexins also play a role in the MAGUK's ability to cluster ion channels at synapses, or is their interaction with members of this protein family restricted to other sites of cell contact? Do extracellular ligands serve as activators or modulators of neurexin's link to the intracellular environment, and how does the extensive alternative splicing in vertebrate neurexins define or modify these interactions? And finally, what, if any, cellular signals can be relayed through the neurexins? These and other questions should inspire many interesting experiments in the near future, as dissection of the role of neurexins in cell junctions is just beginning.

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Model of neurexin interactions in cellular junctions.  (A) Hypothetical junction incorporating a neurexin-gliotactin/ neuroligin interaction with a link to the underlying cytoskeleton  via protein 4.1 and to intracellular signaling/clustering MAGUK  proteins. (B) A similar pathway connects the erythrocyte membrane to the cytoskeleton via glycophorin C. (C) MAGUK members have also been shown to cluster ion channels at synapses. It  is currently unclear if neurexins exist at synapses and are involved in synapse formation, presynaptic vesicle docking, or  postsynaptic channel clustering. Current data favor a role for  neurexins in axonal–glial interactions and cellular junctions instead. Nrxphilin, Neurexophilin; SV, synaptic vesicle; DLG, discs  large protein/PSD95.
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Figure 2: Model of neurexin interactions in cellular junctions. (A) Hypothetical junction incorporating a neurexin-gliotactin/ neuroligin interaction with a link to the underlying cytoskeleton via protein 4.1 and to intracellular signaling/clustering MAGUK proteins. (B) A similar pathway connects the erythrocyte membrane to the cytoskeleton via glycophorin C. (C) MAGUK members have also been shown to cluster ion channels at synapses. It is currently unclear if neurexins exist at synapses and are involved in synapse formation, presynaptic vesicle docking, or postsynaptic channel clustering. Current data favor a role for neurexins in axonal–glial interactions and cellular junctions instead. Nrxphilin, Neurexophilin; SV, synaptic vesicle; DLG, discs large protein/PSD95.

Mentions: Recent in vitro and in vivo studies have provided exciting insights suggesting that the neurexin family may function in organizing cellular junctions. This model is supported by the phenotypic analysis of Drosophila neurexin mutations (2). These mutants lack the ladder-like transcellular septate characteristic of septate junctions. In addition, neurexin is required in glia to form the blood–brain barrier, consistent with an ability of neurexins to form transcellular barriers at cellular junctions. Neurexin also localizes protein 4.1 to sites of cell contact, and neurexin mutations show defects in dorsal closure of the epidermis, a process requiring extensive cellular movements and signaling. Fig. 2 presents a model of a cellular junction incorporating neurexins.


Deciphering the function of neurexins at cellular junctions.

Littleton JT, Bhat MA, Bellen HJ - J. Cell Biol. (1997)

Model of neurexin interactions in cellular junctions.  (A) Hypothetical junction incorporating a neurexin-gliotactin/ neuroligin interaction with a link to the underlying cytoskeleton  via protein 4.1 and to intracellular signaling/clustering MAGUK  proteins. (B) A similar pathway connects the erythrocyte membrane to the cytoskeleton via glycophorin C. (C) MAGUK members have also been shown to cluster ion channels at synapses. It  is currently unclear if neurexins exist at synapses and are involved in synapse formation, presynaptic vesicle docking, or  postsynaptic channel clustering. Current data favor a role for  neurexins in axonal–glial interactions and cellular junctions instead. Nrxphilin, Neurexophilin; SV, synaptic vesicle; DLG, discs  large protein/PSD95.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2139837&req=5

Figure 2: Model of neurexin interactions in cellular junctions. (A) Hypothetical junction incorporating a neurexin-gliotactin/ neuroligin interaction with a link to the underlying cytoskeleton via protein 4.1 and to intracellular signaling/clustering MAGUK proteins. (B) A similar pathway connects the erythrocyte membrane to the cytoskeleton via glycophorin C. (C) MAGUK members have also been shown to cluster ion channels at synapses. It is currently unclear if neurexins exist at synapses and are involved in synapse formation, presynaptic vesicle docking, or postsynaptic channel clustering. Current data favor a role for neurexins in axonal–glial interactions and cellular junctions instead. Nrxphilin, Neurexophilin; SV, synaptic vesicle; DLG, discs large protein/PSD95.
Mentions: Recent in vitro and in vivo studies have provided exciting insights suggesting that the neurexin family may function in organizing cellular junctions. This model is supported by the phenotypic analysis of Drosophila neurexin mutations (2). These mutants lack the ladder-like transcellular septate characteristic of septate junctions. In addition, neurexin is required in glia to form the blood–brain barrier, consistent with an ability of neurexins to form transcellular barriers at cellular junctions. Neurexin also localizes protein 4.1 to sites of cell contact, and neurexin mutations show defects in dorsal closure of the epidermis, a process requiring extensive cellular movements and signaling. Fig. 2 presents a model of a cellular junction incorporating neurexins.

View Article: PubMed Central - PubMed

Affiliation: Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas 77030, USA.

ABSTRACT

Recent in vitro and in vivo studies have provided exciting insights suggesting that the neurexin family may function in organizing cellular junctions. This model is supported by the phenotypic analysis of Drosophila neurexin mutations (2). These mutants lack the ladder-like transcellular septate characteristic of septate junctions. In addition, neurexin is required in glia to form the blood–brain barrier, consistent with an ability of neurexins to form transcellular barriers at cellular junctions. Neurexin also localizes protein 4.1 to sites of cell contact, and neurexin mutations show defects in dorsal closure of the epidermis, a process requiring extensive cellular movements and signaling. Fig. 2 presents a model of a cellular junction incorporating neurexins.

Essential questions remain to be answered concerning the neurexins. Foremost, a precise subcellular location of the known vertebrate neurexins is required to determine if they may also be involved in axonal–glial interactions, similar to that reported for the NRX IV homologue, hNRX IV/Caspr. In addition, it will be important to extend the search for nonneuronal neurexins, as a more complete catalog of the neurexin family is required to begin to determine the variety of roles these proteins might play in cellular junctions. Do neurexins also play a role in the MAGUK's ability to cluster ion channels at synapses, or is their interaction with members of this protein family restricted to other sites of cell contact? Do extracellular ligands serve as activators or modulators of neurexin's link to the intracellular environment, and how does the extensive alternative splicing in vertebrate neurexins define or modify these interactions? And finally, what, if any, cellular signals can be relayed through the neurexins? These and other questions should inspire many interesting experiments in the near future, as dissection of the role of neurexins in cell junctions is just beginning.

Show MeSH
Related in: MedlinePlus