CLASPs Are CLIP-115 and -170 Associating Proteins Involved in the Regional Regulation of Microtubule Dynamics in Motile Fibroblasts

Akhmanova, Anna; Hoogenraad, Casper C.; Drabek, Ksenija; Степанова, Т. Ф.; Dortland, Bjorn; Verkerk, T.; Vermeulen, Wim; Burgering, Boudewijn M.T.; Zeeuw, Chris I. De; Grosveld, Frank; Galjart, Niels

doi:10.1016/s0092-8674(01)00288-4

Cited by 442 publications

(624 citation statements)

References 34 publications

Supporting

Mentioning

586

Contrasting

Order By: Relevance

“…However, it may be noteworthy that MTG16a is often found at the periphery of nucleoli in characteristic rings ( Figure 1g). Interestingly, large arrays of inactive methylated rDNA repeats are also found clustered in perinucleolar chromatin rings (Akhmanova et al, 2000). DNA methylation and histone deacetylation have been shown to be involved in the control of rDNA silencing (Pikaard, 2000;Santoro and Grummt, 2001).…”

Section: Discussionmentioning

confidence: 99%

The transcriptional corepressor MTG16a contains a novel nucleolar targeting sequence deranged in t (16; 21)-positive myeloid malignancies

et al. 2002

View full text Add to dashboard Cite

The MTG (Myeloid Translocation Gene) proteins are a family of novel transcriptional corepressors. We report that MTG16a, a protein isoform encoded by the MTG16 gene deranged by the t (16; 21) in myeloid malignancies, is targeted to the nucleolus. The amino acid sequence necessary for nucleolar localization was mapped to the MTG16a N-terminal region. MTG16a, like MTG8, the nuclear corepressor deranged by the t (8; 21), is capable to interact with specific histone deacetylases (HDACs) suggesting that the protein may mediate silencing of nucleolar gene transcription. In addition, MTG16a is capable to form oligomers with other MTG proteins. As a consequence of the t (16; 21) the AML1 DNA-binding domain replaces the MTG16a N-terminal region. The AML1-MTG16 fusion protein is targeted to the nucleoplasm where it is capable to oligomerize with MTG16a and interact with HDAC1 and HDAC3. The deficiency of HDAC-containing complexes at nucleolar sites and the accumulation of HDAC-containing complexes at AML1-sites may be critical in the pathogenesis of t (16; 21) myeloid malignancies.

show abstract

Section: Discussionmentioning

confidence: 99%

The transcriptional corepressor MTG16a contains a novel nucleolar targeting sequence deranged in t (16; 21)-positive myeloid malignancies

et al. 2002

View full text Add to dashboard Cite

show abstract

“…An expression vector for glycosyltransferase (GT)-EGFP (a gift from M. Murata, The University of Tokyo) was used for Golgi visualization 34 . Expression vectors for EGFP-CLSAP2 (a gift from A. Akhmanova, The Utrecht University, The Netherlands) 19 and Flag-AKAP450/CG-NAP 30 were used for co-immunoprecipitation with MTCL1. Cell culture and transfections.…”

Section: Methodsmentioning

confidence: 99%

“…As the KR-rich region resides outside of the central coiled-coil region that mediates MTCL1 oligomerization 15 , this region may indirectly induce MT bundling through its MT-stabilizing activity as has been shown for Taxol and various MT plus-end tracking proteins 18,19 . In fact, when overexpressed in HeLa-K cells, the KR-rich region was sufficient to enrich the acetylated tubulin in the MT bundles, which it co-localized with (see EGFP-KR in Fig.…”

mentioning

confidence: 95%

MTCL1 crosslinks and stabilizes non-centrosomal microtubules on the Golgi membrane

et al. 2014

View full text Add to dashboard Cite

Recent studies have revealed the presence of a microtubule subpopulation called Golgi-derived microtubules that support Golgi ribbon formation, which is required for maintaining polarized cell migration. CLASPs and AKAP450/CG-NAP are involved in their formation, but the underlying molecular mechanisms remain unclear. Here, we find that the microtubule-crosslinking protein, MTCL1, is recruited to the Golgi membranes through interactions with CLASPs and AKAP450/CG-NAP, and promotes microtubule growth from the Golgi membrane. Correspondingly, MTCL1 knockdown specifically impairs the formation of the stable perinuclear microtubule network to which the Golgi ribbon tethers and extends. Rescue experiments demonstrate that besides its crosslinking activity mediated by the N-terminal microtubule-binding region, the C-terminal microtubule-binding region plays essential roles in these MTCL1 functions through a novel microtubule-stabilizing activity. These results suggest that MTCL1 cooperates with CLASPs and AKAP450/CG-NAP in the formation of the Golgi-derived microtubules, and mediates their development into a stable microtubule network.

show abstract

“…Collapsin response mediator protein 2 (CRMP-2), a recently identified protein that binds to tubulin dimer and promotes microtubule polymerization, has been shown to be negatively regulated by GSK-3 phosphorylation (Yoshimura et al 2005). Similarly, the ability of two microtubule plus end binding proteins, APC and CLIP-associated proteins (CLASP) to stabilize microtubules is also abolished by GSK-3 phosphorylation (Akhmanova et al 2001;. Finally, MAP-1b that functions to maintain microtubule dynamics is also regulated by GSK-3 (Trivedi et al 2005).…”

Section: Gsk-3b and Axonal Microtubule Regulationmentioning

confidence: 99%

Intracellular control of developmental and regenerative axon growth

Zhou

Snider

2006

Phil. Trans. R. Soc. B

174

138

View full text Add to dashboard Cite

Axon growth is a highly regulated process that requires stimulating signals from extracellular factors. The extracellular signals are then transduced to regulate coordinately gene expression and local axon assembly. Growth factors, especially neurotrophins that act via receptor tyrosine kinases, have been heavily studied as extracellular factors that stimulate axon growth. Downstream of receptor tyrosine kinases, recent studies have suggested that phosphatidylinositol-3 kinase (PI3K) regulates local assembly of axonal cytoskeleton, especially microtubules, via glycogen synthase kinase 3b (GSK-3b) and multiple microtubule binding proteins. The role of extracellular signal regulated kinase (ERK) signalling in regulation of local axon assembly is less clear, but may involve the regulation of local protein translation. Gene expression during axon growth is regulated by transcription factors, among which cyclic AMP response element binding protein and nuclear factors of activated T-cells (NFATs) are known to be required for neurotrophin (NT)-induced axon extension. In addition to growth factors, extracellular matrix molecules and neuronal activity contribute importantly to control axon growth. Increasingly, evidence suggests that these influences act to enhance growth via coordinating with growth factor signalling. Finally, evidence is emerging that developmental versus regenerative axon growth may be mediated by distinct signalling pathways, both at the level of gene transcription and at the level of local axon assembly.

show abstract

CLASPs Are CLIP-115 and -170 Associating Proteins Involved in the Regional Regulation of Microtubule Dynamics in Motile Fibroblasts

Cited by 442 publications

References 34 publications

The transcriptional corepressor MTG16a contains a novel nucleolar targeting sequence deranged in t (16; 21)-positive myeloid malignancies

The transcriptional corepressor MTG16a contains a novel nucleolar targeting sequence deranged in t (16; 21)-positive myeloid malignancies

MTCL1 crosslinks and stabilizes non-centrosomal microtubules on the Golgi membrane

Intracellular control of developmental and regenerative axon growth

Contact Info

Product

Resources

About