Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0344329 (collapse)
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We have studied asteroid bodies (ABs) of multinucleated giant cells (MGCs) in a series of sarcoid and foreign body granulomas with a standard streptavidin-biotin peroxidase technique, using commercial antibodies against collagen, vimentin and tubulin on routinely processed tissue as well as, in one case, on fresh frozen sections (FS). Our findings clearly indicate that ABs are products of the microtubule (MT) system and lack collagen. The tubulin in them stains in fresh FS but is "masked" in formalin-fixed tissue. It can be fully "unmasked" by dephosphorylation and partially by trypsinization. Compared to single microtubule organizing centers (MTOCs) in mononuclear cells serving as internal controls, ABs are obvious replicas of centrosome-nucleated MT assemblies from which they differ principally by the disproportionate size of their components and by the invariable vacuolation of the surrounding cytoplasm. Relying on bits of relevant information gleaned from the literature, our observations support the following preliminary conclusions: 1) spokes are massive bundles of MTs rich in tyrosinated alpha-tubulin coassembled in phosphorylated linkages with yet unidentified microtubule associated proteins (MAPs) and probably microfilament proteins; cores are masses of pericentriolar material including amorphous tubulins, MAPs, phosphoproteins and phospholipids; 2) their size, at least in some ABs, appears to indicate the presence of overlapping centrosome-nucleated MTOCs which in monocyte-derived MGCs are known to be multiple; 3) the cytoplasmic vacuolations around them reflect a collapse and retraction of intermediate filaments (IFs), indicating substantial ongoing MT depolymerization with disruption of MT-IF interactions; 4) ABs are products of unusual MTOC dynamics characterized by simultaneous MT assembly and depolymerization; such a phenomenon, termed "microtubule catastrophe", has been recognized in vitro with centrosome-nucleated MT assemblies under conditions of low tubulin concentrations.
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PMID:Asteroid bodies: products of unusual microtubule dynamics in monocyte-derived giant cells. An immunohistochemical study. 789 35

Posttranslationally modified forms of tubulin accumulate in the subset of stabilized microtubules (MTs) in cells but are not themselves involved in generating MT stability. We showed previously that stabilized, detyrosinated (Glu) MTs function to localize vimentin intermediate filaments (IFs) in fibroblasts. To determine whether tubulin detyrosination or MT stability is the critical element in the preferential association of IFs with Glu MTs, we microinjected nonpolymerizable Glu tubulin into cells. If detyrosination is critical, then soluble Glu tubulin should be a competitive inhibitor of the IF-MT interaction. Before microinjection, Glu tubulin was rendered nonpolymerizable and nontyrosinatable by treatment with iodoacetamide (IAA). Microinjected IAA-Glu tubulin disrupted the interaction of IFs with MTs, as assayed by the collapse of IFs to a perinuclear location, and had no detectable effect on the array of Glu or tyrosinated MTs in cells. Conversely, neither IAA-tyrosinated tubulin nor untreated Glu tubulin, which assembled into MTs, caused collapse of IFs when microinjected. The epitope on Glu tubulin responsible for interfering with the Glu MT-IF interaction was mapped by microinjecting tubulin fragments of alpha-tubulin. The 14-kDa C-terminal fragment of Glu tubulin (alpha-C Glu) induced IF collapse, whereas the 36-kDa N-terminal fragment of alpha-tubulin did not alter the IF array. The epitope required more than the detyrosination site at the C terminus, because a short peptide (a 7-mer) mimicking the C terminus of Glu tubulin did not disrupt the IF distribution. We previously showed that kinesin may mediate the interaction of Glu MTs and IFs. In this study we found that kinesin binding to MTs in vitro was inhibited by the same reagents (i.e., IAA-Glu tubulin and alpha-C Glu) that disrupted the IF-Glu MT interaction in vivo. These results demonstrate for the first time that tubulin detyrosination functions as a signal for the recruitment of IFs to MTs via a mechanism that is likely to involve kinesin.
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PMID:Detyrosination of tubulin regulates the interaction of intermediate filaments with microtubules in vivo via a kinesin-dependent mechanism. 1019 60