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Query: UMLS:C0344329 (collapse)
 28,634 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The adult mammalian CNS has a limited capacity for nerve regeneration and structural plasticity. The presence of glia-derived inhibitory factors myelin-associated glycoprotein (MAG) and Nogo-A have been suggested to provide a nonpermissive environment for elongating nerve fibers. In particular, Nogo-A, an integral membrane protein predominantly expressed by oligodendrocytes, has been demonstrated to impair neurite growth in vitro and in vivo. Structure function analysis revealed that Nogo-A protein contains at least two active domains, NiG and Nogo-66, with diverse effects on neurite outgrowth and cell spreading. We now provide evidence that these inhibitory domains mediate their effects via an antagonistic regulation of the small GTPases RhoA and Rac1, resulting in activation of RhoA and suppression of Rac1. By inactivating RhoA with C3 transferase or the downstream effector Rho-kinase ROCK with, the inhibitory effects of both Nogo-A fragments and MAG on neurite outgrowth and oligodendrocyte-mediated growth cone collapse were abolished. Furthermore, we show that the recently cloned receptor for Nogo-66 and MAG, NgR, is not necessary for either NiG- or MAG-induced RhoA activation.
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PMID:Nogo-A and myelin-associated glycoprotein mediate neurite growth inhibition by antagonistic regulation of RhoA and Rac1. 1245 Nov 36

The NG2 chondroitin sulfate proteoglycan, an integral membrane proteoglycan, inhibits axon growth from cerebellar granule neurons and dorsal root ganglia (DRG) neurons in vitro. The extracellular domain of the NG2 core protein contains three subdomains: an N-terminal globular domain (domain 1), a central extended domain that has the sites for glycosaminoglycan (GAG) attachment (domain 2), and a juxtamembrane domain (domain 3). Here, we used domain-specific fusion proteins and antibodies to map the inhibitory activity within the NG2 core protein. Fusion proteins encoding domain 1 (D1-Fc) or domain 3 (D3-Fc) of NG2 inhibited axon growth from cerebellar granule neurons when the proteins were substrate-bound. These proteins also induced growth cone collapse from newborn DRG neurons when added to the culture medium. Domain 2 only inhibited axon growth when the GAG chains were present. Neutralizing antibodies directed against domain 1 or 3 blocked completely the inhibition from substrates coated with D1-Fc or D3-Fc. When the entire extracellular domain of NG2 was used as a substrate, however, both neutralizing antibodies were needed to reverse completely the inhibition. When NG2 was expressed on the surface of HEK293 cells, the neutralizing anti-D1 antibody was sufficient to block the inhibition, whereas the anti-D3 antibody had no effect. These results suggest that domains 1 and 3 of NG2 can inhibit neurite growth independently. These inhibitory domains may be differentially exposed depending on whether NG2 is presented as an integral membrane protein or as a secreted protein associated with the extracellular matrix.
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PMID:Multiple regions of the NG2 proteoglycan inhibit neurite growth and induce growth cone collapse. 1251 14

The microtubule-binding 63-kDa cytoskeleton-linking membrane protein (CLIMP-63) is an integral membrane protein that links the endoplasmic reticulum (ER) to microtubules. Here, we tested whether this interaction is regulated by phosphorylation. Metabolic labeling with (32)P showed that CLIMP-63 is a phosphoprotein with increased phosphorylation during mitosis. CLIMP-63 of mitotic cells is unable to bind to microtubules in vitro. Mitotic phosphorylation can be prevented by mutation of serines 3, 17, and 19 in the cytoplasmic domain of CLIMP-63. When these residues are mutated to glutamic acid, and hence mimic mitotic phosphorylation, CLIMP-63 does no longer bind to microtubules in vitro. Overexpression of the phospho-mimicking mitotic form of CLIMP-63 in interphase cells leads to a collapse of the ER around the nucleus, leaving the microtubular network intact. The results suggest that CLIMP-63-mediated stable anchoring of the ER to microtubules is required to maintain the spatial distribution of the ER during interphase and that this interaction is abolished by phosphorylation of CLIMP-63 during mitosis.
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PMID:Phosphorylation controls CLIMP-63-mediated anchoring of the endoplasmic reticulum to microtubules. 1570 17

In structural biology, collision cross sections (CCSs) from ion mobility mass spectrometry (IM-MS) measurements are routinely compared to computationally or experimentally derived protein structures. Here, we investigate whether CCS data can inform about the shape of a protein in the absence of specific reference structures. Analysis of the proteins in the CCS database shows that protein complexes with low apparent densities are structurally more diverse than those with a high apparent density. Although assigning protein shapes purely on CCS data is not possible, we find that we can distinguish oblate- and prolate-shaped protein complexes by using the CCS, molecular weight, and oligomeric states to mine the Protein Data Bank (PDB) for potentially similar protein structures. Furthermore, comparing the CCS of a ferritin cage to the solution structures in the PDB reveals significant deviations caused by structural collapse in the gas phase. We then apply the strategy to an integral membrane protein by comparing the shapes of a prokaryotic and a eukaryotic sodium/proton antiporter homologue. We conclude that mining the PDB with IM-MS data is a time-effective way to derive low-resolution structural models.
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PMID:Predicting the Shapes of Protein Complexes through Collision Cross Section Measurements and Database Searches. 3266 Feb 38