Ligand-Dependent Recruitment of the ErbB4 Signaling Complex into Neuronal Lipid Rafts

Ma, Le; Huang, Yang; Pitcher, Graham; Valtschanoff, Juli G.; Ying, Howard S.; Feng, Lin; Lu, Bai; Xiong, Wen-Cheng; Salter, Michael W.; Weinberg, Richard J.; Mei, Lin

doi:10.1523/jneurosci.23-08-03164.2003

Cited by 122 publications

(132 citation statements)

References 78 publications

(114 reference statements)

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“…Moreover, disruption of lipid rafts inhibits NRG-induced activation of ERK and prevents NRG-induced blockade of long-term potentiation at synapses in hippocampal slices (Ma et al 2003).…”

Section: Function Of Lipid Rafts In Neural Cellsmentioning

confidence: 97%

“…ErbB4, a member of the RTK family that binds neuregulin (NRG), also localizes to lipid rafts in a ligand-dependent manner in primary cortical neuronal cultures and human embryonic kidney (HEK293) cells (Ma et al 2003). Moreover, disruption of lipid rafts inhibits NRG-induced activation of ERK and prevents NRG-induced blockade of long-term potentiation at synapses in hippocampal slices (Ma et al 2003).…”

Section: Function Of Lipid Rafts In Neural Cellsmentioning

confidence: 99%

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Directing traffic in neural cells: determinants of receptor tyrosine kinase localization and cellular responses

Romanelli

Wood²

2008

Journal of Neurochemistry

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The trafficking of receptor tyrosine kinases (RTKs) to distinct subcellular locations is essential for the specificity and fidelity of signal transduction and biological responses. This is particularly important in the PNS and CNS in which RTKs mediate key events in the development and maintenance of neurons and glia through a wide range of neural processes, including survival, proliferation, differentiation, neurite outgrowth, and synaptogenesis. The mechanisms that regulate the targeting of RTKs to their subcellular destinations for appropriate signal transduction, however, are still elusive. In this review, we discuss evidence for the spatial organization of signaling machinery into distinct subcellular compartments, as well as the role for ligand specificity, receptor sorting signals, and lipid raft microdomains in RTK targeting and the resultant cellular responses in neural cells.

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“…Moreover, disruption of lipid rafts inhibits NRG-induced activation of ERK and prevents NRG-induced blockade of long-term potentiation at synapses in hippocampal slices (Ma et al 2003).…”

Section: Function Of Lipid Rafts In Neural Cellsmentioning

confidence: 97%

Section: Function Of Lipid Rafts In Neural Cellsmentioning

confidence: 99%

Directing traffic in neural cells: determinants of receptor tyrosine kinase localization and cellular responses

Romanelli

Wood²

2008

Journal of Neurochemistry

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“…In the CNS, neuregulin stimulates recruit-ment of ErbB4 and Grb2 to neuronal lipid rafts. 203 Grb2 involvement in neuronal signalling is thus directly modulated by neuregulin, and DISC1 function may turn out to be similarly influenced by neuregulin and vice versa through its interaction with Grb2.…”

Section: Disc1 Interaction With Grb2mentioning

confidence: 99%

The DISC locus in psychiatric illness

et al. 2007

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The DISC locus is located at the breakpoint of a balanced t(1;11) chromosomal translocation in a large and unique Scottish family. This translocation segregates in a highly statistically significant manner with a broad diagnosis of psychiatric illness, including schizophrenia, bipolar disorder and major depression, as well as with a narrow diagnosis of schizophrenia alone. Two novel genes were identified at this locus and due to the high prevalence of schizophrenia in this family, they were named Disrupted-in-Schizophrenia-1 (DISC1) and Disrupted-in-Schizophrenia-2 (DISC2). DISC1 encodes a novel multifunctional scaffold protein, whereas DISC2 is a putative noncoding RNA gene antisense to DISC1. A number of independent genetic linkage and association studies in diverse populations support the original linkage findings in the Scottish family and genetic evidence now implicates the DISC locus in susceptibility to schizophrenia, schizoaffective disorder, bipolar disorder and major depression as well as various cognitive traits. Despite this, with the exception of the t(1;11) translocation, robust evidence for a functional variant(s) is still lacking and genetic heterogeneity is likely. Of the two genes identified at this locus, DISC1 has been prioritized as the most probable candidate susceptibility gene for psychiatric illness, as its protein sequence is directly disrupted by the translocation. Much research has been undertaken in recent years to elucidate the biological functions of the DISC1 protein and to further our understanding of how it contributes to the pathogenesis of schizophrenia. These data are the main subject of this review; however, the potential involvement of DISC2 in the pathogenesis of psychiatric illness is also discussed. A detailed picture of DISC1 function is now emerging, which encompasses roles in neurodevelopment, cytoskeletal function and cAMP signalling, and several DISC1 interactors have also been defined as independent genetic susceptibility factors for psychiatric illness. DISC1 is a hub protein in a multidimensional risk pathway for major mental illness, and studies of this pathway are opening up opportunities for a better understanding of causality and possible mechanisms of intervention. Molecular Psychiatry (2008) 13, 36-64; doi:10.1038/sj.mp.4002106; published online 2 October 2007 Keywords: schizophrenia; bipolar disorder; depression; DISC1; DISC2; mouse models Genetics of DISC1 discoverySt Clair et al. 1 first reported a Scottish family with a high loading of major mental illness, which cosegregates with a t(1;11) translocation. Long-term follow-up of this family over a period of 30 years has reported 87 family members, of whom 37 carry the translocation. 2 Of 29 individuals carrying the translocation, for whom psychiatric assessment was possible, 7 have a diagnosis of schizophrenia, 1 has a diagnosis of bipolar disorder and 10 cases of recurrent major depression were also reported. 2 Thus, 18 of 29 translocation carriers are diagnosed with major mental illness whereas none of...

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“…For example, lipid rafts are necessary for signaling pathways initiated by IgE (Baird et al, 1999), T-cell antigen receptor activation (Janes et al, 2001), and glial cell line-derived neurotrophic factor receptor activation (Tansey et al, 2001). In the nerve system, disruption of lipid rafts prevents neurons from responding properly to trophic factors, including neuregulin and BDNF (Ma et al, 2003;Suzuki et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Lipid Rafts Serve as a Signaling Platform for Nicotinic Acetylcholine Receptor Clustering

Zhu¹,

Xiong²,

Mei³

2006

J. Neurosci.

130

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Agrin, a motoneuron-derived factor, and the muscle-specific receptor tyrosine kinase (MuSK) are essential for the acetylcholine receptor (AChR) clustering at the postjunctional membrane. However, the underlying signaling mechanisms remain poorly defined. We show that agrin stimulates a dynamic translocation of the AChR into lipid rafts-cholesterol and sphingolipid-rich microdomains in the plasma membrane. This follows MuSK partition into lipid rafts and requires its activation. Disruption of lipid rafts inhibits MuSK activation and downstream signaling and AChR clustering in response to agrin. Rapsyn, an intracellular protein necessary for AChR clustering, is located constitutively in lipid rafts, but its interaction with the AChR is inhibited when lipid rafts are perturbed. These results reveal that lipid rafts may regulate AChR clustering by facilitating the agrin/MuSK signaling and the interaction between the receptor and rapsyn, both necessary for AChR clustering and maintenance. These results provide insight into mechanisms of AChR cluster formation.

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Ligand-Dependent Recruitment of the ErbB4 Signaling Complex into Neuronal Lipid Rafts

Cited by 122 publications

References 78 publications

Directing traffic in neural cells: determinants of receptor tyrosine kinase localization and cellular responses

Directing traffic in neural cells: determinants of receptor tyrosine kinase localization and cellular responses

The DISC locus in psychiatric illness

Lipid Rafts Serve as a Signaling Platform for Nicotinic Acetylcholine Receptor Clustering

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