Neurobeachin Is Essential for Neuromuscular Synaptic Transmission

Su, Yongxuan; Balice-Gordon, Rita J.; Hess, Darren; Landsman, Douglas; Minarcik, Jeremy; Golden, Jeffrey A.; Hurwitz, Ivy; Liebhaber, Stephen A.; Cooke, Nancy E.

doi:10.1523/jneurosci.4644-03.2004

Cited by 74 publications

(104 citation statements)

References 47 publications

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“…Defects in synapse morphology, enrichment of synaptic molecules, and synaptic transmission were described in two Nbea knockout (KO) mouse lines (Su et al, 2004;Medrihan et al, 2009;Niesmann et al, 2011). We now demonstrate that defects in the synaptic localization of ionotropic receptors for the key excitatory and inhibitory neurotransmitters are a major cause of these defects and that, in the absence of Nbea, these receptors accumulate in the biosynthetic pathway.…”

Section: Less Functional Neurotransmitter Receptors At Nbea Ko Synapsesmentioning

confidence: 68%

“…As Nbea KO mice die perinatally (Su et al, 2004;Medrihan et al, 2009), we used autaptic and high-density cultures of hippocampal and striatal neurons from E18 embryos to study the functional consequences of Nbea KO. We detected no significant morphological or functional differences between wild-type (WT) and heterozygous Nbea KO neurons (Fig.…”

Section: Defective Glutamatergic and Gabaergic Synaptic Transmission mentioning

confidence: 99%

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Neurobeachin regulates neurotransmitter receptor trafficking to synapses

Nair¹,

Lauks²,

Jung³

et al. 2013

J Gen Physiol

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Section: Less Functional Neurotransmitter Receptors At Nbea Ko Synapsesmentioning

confidence: 68%

Section: Defective Glutamatergic and Gabaergic Synaptic Transmission mentioning

confidence: 99%

Neurobeachin regulates neurotransmitter receptor trafficking to synapses

Nair¹,

Lauks²,

Jung³

et al. 2013

J Gen Physiol

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“…However, Nbea-deficient mice die shortly after birth because of respiratory problems; thus, the role of Nbea in associative learning is as yet untested (Su et al, 2004;Medrihan et al, 2009). To test whether Drosophila rugose functions in learning and memory, we used the well-established olfactory conditioning paradigm (Tully and Quinn, 1985).…”

Section: Resultsmentioning

confidence: 99%

“…Drosophila Rg is neuronally expressed in the larval and adult CNS and localizes to the TGN and endomembranes near the TGN, as does NBEA in mammals (Wang et al, 2000). In contrast to Nbea knock-out mice that die shortly after birth (Su et al, 2004;Medrihan et al, 2009), loss of Rg function results in viable and fertile adults that display an increased number of synaptic boutons at the level of the larval NMJ without affecting basal synaptic transmission. At the level of CNS development, Drosophila rg mutants display gross morphological defects of the Drosophila MB, the fly "learning center," and at the same time rg mutants are impaired in associative odor learning.…”

Section: Discussionmentioning

confidence: 99%

“…NBEA is a multidomain scaffolding protein with an AKAP (A-kinase anchor protein) domain and is localized near the transGolgi network (TGN) (Wang et al, 2000), supporting a function in vesicle sorting or secretion as demonstrated by experiments performed in Nbea knock-out mice and in vitro (Wang et al, 2000;Su et al, 2004;Medrihan et al, 2009;Castermans et al, 2010;Niesmann et al, 2011). Whereas NBEA is known for its neuronal function and its implication in autism spectrum disorders (Castermans et al, 2003;Volders et al, 2011), the human homolog LRBA has a broad expression pattern, and its function is currently unknown (Wang et al, 2001).…”

Section: Introductionmentioning

confidence: 95%

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Drosophila rugoseIs a Functional Homolog of MammalianNeurobeachinand Affects Synaptic Architecture, Brain Morphology, and Associative Learning

Volders

Scholz²,

Slabbaert

et al. 2012

J. Neurosci.

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Neurobeachin (Nbea) is implicated in vesicle trafficking in the regulatory secretory pathway, but details on its molecular function are currently unknown. We have used Drosophila melanogaster mutants for rugose (rg), the Drosophila homolog of Nbea, to further elucidate the function of this multidomain protein. Rg is expressed in a granular pattern reminiscent of the Golgi network in neuronal cell bodies and colocalizes with transgenic Nbea, suggesting a function in secretory regulation. In contrast to Nbea Ϫ/Ϫ mice, rg null mutants are viable and fertile and exhibit aberrant associative odor learning, changes in gross brain morphology, and synaptic architecture as determined at the larval neuromuscular junction. At the same time, basal synaptic transmission is essentially unaffected, suggesting that structural and functional aspects are separable. Rg phenotypes can be rescued by a Drosophila rg؉ transgene, whereas a mouse Nbea transgene rescues aversive odor learning and synaptic architecture; it fails to rescue brain morphology and appetitive odor learning. This dissociation between the functional redundancy of either the mouse or the fly transgene suggests that their complex composition of numerous functional and highly conserved domains support independent functions. We propose that the detailed compendium of phenotypes exhibited by the Drosophila rg null mutant provided here will serve as a test bed for dissecting the different functional domains of BEACH (for beige and human Chediak-Higashi syndrome) proteins, such as Rugose, mouse Nbea, or Nbea orthologs in other species, such as human.

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Disabled‐1 is a large common fragile site gene, inactivated in multiple cancers

McAvoy

Zhu

Perez

et al. 2007

Genes Chromosomes & Cancer

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Common fragile sites (CFS) are large, genomically unstable regions, which are hot-spots for deletions and other alterations, especially in cancer cells. Several have been shown to contain genes that span large genomic regions, such as FHIT (1.5 Mb), WWOX (1.0 Mb), GRID2 (1.36 Mb), PARK2 (1.3 Mb), and RORA (730 kb). These genes are frequently inactivated in multiple different cancers, and FHIT and WWOX are shown to function as tumor suppressors. The disabled-1 gene (DAB1) is one of the human homologs of the Drosophila disabled locus, which in mammals is involved in neuronal migration and lamination in the developing cerebral cortex. Mice DAB1 inactivation results in the neurological mutant Scrambler, having similarities to mice with the inactivation of PARK2 (Quaker), GRID2 (Lurcher), and RORA (Staggerer). We were interested in whether DAB1 was another large CFS gene that could have cancer development importance. We demonstrated here that the human DAB1 gene (spanning 1.25 Mb) mapped within FRA1B CFS region on chromosomal band 1p32.2. Real-time RT-PCR analysis revealed that the expression level of DAB1 was decreased in many human cancer samples, including primary tumor tissues and cancer-derived cell lines, from several different cancers, especially in brain and endometrial cancer. Additionally, the introduction of an over-expression DAB1 plasmid into two different cell lines, having insignificant endogenous DAB1 expression, resulted in decreased cell growth. In summary, DAB1 is another gene that resides within an unstable CFS region and might play a role in human tumorigenesis. These data may provide further linkage between neurological development and cancer.

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Neurobeachin Is Essential for Neuromuscular Synaptic Transmission

Cited by 74 publications

References 47 publications

Neurobeachin regulates neurotransmitter receptor trafficking to synapses

Neurobeachin regulates neurotransmitter receptor trafficking to synapses

Drosophila rugoseIs a Functional Homolog of MammalianNeurobeachinand Affects Synaptic Architecture, Brain Morphology, and Associative Learning

Disabled‐1 is a large common fragile site gene, inactivated in multiple cancers

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