CLIP-115, a Novel Brain-Specific Cytoplasmic Linker Protein, Mediates the Localization of Dendritic Lamellar Bodies

The transcriptional regulation of the Hoxc8 gene is controlled during early mouse embryogenesis by an enhanceosome-like control region, termed the early enhancer (EE), located 3 kb upstream from the Hoxc8 translation start site. The EE is involved in establishing the posterior expression pattern of Hoxc8 at embryonic day (E) 8.5-9.0. Genetic and biochemical data have shown that nuclear factors interact with this region in a sequence-specific manner. We have used a yeast onehybrid screen in a search for transcription factors that bind to EE motifs and have isolated a novel murine DNA-binding protein, termed BEN (binding factor for early enhancer). The ORF of BEN encodes a protein of 1072 amino acids and contains six helix-loop-helix domains, a hydrophobic leucine zipper-like motif, and a serine-rich repeat. The murine BEN gene is structurally similar to the human gene TFII-I in that both genes encode unique 95-amino acid long helixloop͞span-helix domains. The BEN gene produces several major transcripts (3.6, 4.4, and 5.9 kb) present in most adult tissues and shows discrete spatial and temporal domains of expression in areas of epithelial-mesenchymal interaction during mouse embryogenesis from E9.5 to E12.5. Several BEN-encoded polypeptides of different sizes ranging from 165 to 40 kDa were identified by Western blot analysis using BEN-specific polyclonal Abs. We propose, on the bases of sequence homology, that BEN is the mouse ortholog of the recently described human gene, WBSCR11, known also as GTF2IRD1, GTF3, Cream1, and MusTRD1. This gene is deleted hemizygously in individuals with Williams Syndrome, an autosomal dominant genetic condition characterized by complex physical, cognitive, and behavioral traits resulting from a perturbed developmental process.Williams Syndrome ͉ Hoxc8

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“…The other is CLIP-115, reported to link specific cellular organelles to the cytoskeleton via microtubules (38).…”

Section: Discussionmentioning

confidence: 99%

Isolation and characterization of BEN, a member of the TFII-I family of DNA-binding proteins containing distinct helix–loop–helix domains

Bayarsaihan

Ruddle

2000

Proc. Natl. Acad. Sci. U.S.A.

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“…As such, CLIP-170 mediates the interaction of endocytic carrier vesicles to microtubules [Pierre et al, 1992]. CLIP-115 is responsible for the polarized distribution of the dendritic lamellar bodies (DLB) in neurons by anchoring them to the dendritic microtubules [De Zeeuw et al, 1997;Hoogenraad et al, 2000]. Recently, a new class of proteins termed CLASPs (CLIP-associated proteins) was identified [Akhmanova et al, 2001].…”

Section: Segregation Of Rer Membranes In the Somato-dendritic Compartmentioning

confidence: 99%

HMWMAP2: New perspectives on a pathway to dendritic identity

Farah

Leclerc

2008

Cell Motil. Cytoskeleton

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Neuronal polarity is established by the differentiation of two types of cytoplasmic processes: dendrites and the axon. These processes can be distinguished by their composition in microtubule-associated proteins, the high molecular weight MAP2 proteins (HMWMAP2) being found in the dendrites and tau proteins in the axon. It is believed that the main contribution of HMWMAP2 to the acquisition and maintenance of dendrites is to promote microtubule assembly and stability. However, recent studies force us to enlarge our view on how HMWMAP2 might contribute to defining the role of the dendritic microtubules. The purpose of this article is to convey our view that HMWMAP2 are important players in defining the contribution of microtubules to dendritic identity by anchoring membranous organelles and signaling proteins to the dendritic microtubules and by being a receptor for neurosteroids. Cell Motil. Cytoskeleton 65: 515-527, 2008. '

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“…As such, CLIP-170 has been reported to mediate the interaction of endocytic carrier vesicles to microtubules (33). Furthermore, CLIP-115 was shown to be responsible for the polarized distribution of the dendritic lamellar bodies in neurons (34,35). Recently, a new class of proteins termed CLASPs (CLIP-associated proteins) was identified (76).…”

Section: Fig 8 In Vitro Reconstitution Of the Er-map2-microtubule Cmentioning

confidence: 99%

“…In recent years, families of proteins called CLIPs and Hooks were shown to mediate the interaction between microtubules and membranous organelles (33)(34)(35)(36). Most interestingly, CLIP-115 was found to be responsible for the polarized distribution of a membranous organelle exclusively present in dendrites termed the dendritic lamellar bodies (34).…”

mentioning

confidence: 99%

Interaction of Microtubule-associated Protein-2 and p63

Farah

Liazoghli

Perreault

et al. 2005

Journal of Biological Chemistry

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Neurons are polarized cells presenting two distinct compartments, dendrites and an axon. Dendrites can be distinguished from the axon by the presence of rough endoplasmic reticulum (RER). The mechanism by which the structure and distribution of the RER is maintained in these cells is poorly understood. In the present study, we investigated the role of the dendritic microtubuleassociated protein-2 (MAP2) in the RER membrane positioning by comparing their distribution in brain subcellular fractions and in primary hippocampal cells and by examining the MAP2-microtubule interaction with RER membranes in vitro. Subcellular fractionation of rat brain revealed a high MAP2 content in a subfraction enriched with the endoplasmic reticulum markers ribophorin and p63. Electron microscope morphometry confirmed the enrichment of this subfraction with RER membranes. In cultured hippocampal neurons, MAP2 and p63 were found to concomitantly compartmentalize to the dendritic processes during neuronal differentiation. Protein blot overlays using purified MAP2c protein revealed its interaction with p63, and immunoprecipitation experiments performed in HeLa cells showed that this interaction involves the projection domain of MAP2. In an in vitro reconstitution assay, MAP2-containing microtubules were observed to bind to RER membranes in contrast to microtubules containing tau, the axonal MAP. This binding of MAP2c microtubules was reduced when an anti-p63 antibody was added to the assay. The present results suggest that MAP2 is involved in the association of RER membranes with microtubules and thereby could participate in the differential distribution of RER membranes within a neuron.Neurons are polarized cells that present two distinct compartments, dendrites and an axon. These compartments can be distinguished by their morphology; dendrites are multiple and taper, whereas the axon is unique and its diameter is uniform (1-4). Dendrites and axon also differ by their membranous organelle composition; RER 1 is found in the somato-dendritic compartment but not in the axon, and the number of free ribosomes is a lot higher in dendrites than in the axon (1, 2, 5). The cytoskeletal elements are also distinctly distributed in these neuronal compartments; the number of microtubules is higher in dendrites than in the axon, whereas the opposite is noted for neurofilaments (1, 2, 6).Microtubules are involved in the establishment of cell polarity. Notably, the microtubules of dendrites and axon contain different microtubule-associated proteins (MAPs); the microtubule-associated protein-2 (MAP2) is found in dendrites, whereas tau is present only in the axon (6 -8). The contribution of these MAPs to the establishment of neuronal polarity has been well documented. Tau contributes to the axonal differentiation in primary neuronal cultures, whereas MAP2 is involved in the differentiation of minor neurites, the neuronal processes that become dendrites, and in the maintenance of dendrites in adult neurons (9 -14). Despite the fact that MAP2 and tau are...

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CLIP-115, a Novel Brain-Specific Cytoplasmic Linker Protein, Mediates the Localization of Dendritic Lamellar Bodies

Cited by 91 publications

References 46 publications

Isolation and characterization of BEN, a member of the TFII-I family of DNA-binding proteins containing distinct helix–loop–helix domains

Isolation and characterization of BEN, a member of the TFII-I family of DNA-binding proteins containing distinct helix–loop–helix domains

HMWMAP2: New perspectives on a pathway to dendritic identity

Interaction of Microtubule-associated Protein-2 and p63

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