Gene/Protein Disease Symptom Drug Enzyme Compound
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 28,634 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neuronal morphogenesis is regulated, among other factors, by microtubule-associated proteins (MAPs). A family of these proteins, MAP2, which is very abundant in the mammalian nervous system, has been associated with the formation of neurites at early developmental stages and with the dendritic scaffold upon maturation. The function of MAP2 is regulated by its phosphorylation state. One of the phosphorylation sites that has been described is located in the proline-rich region of the protein. It comprises of the residues 1616-1626 and is specifically recognized by the antibody 305. However, little is known about the functional consequences of its modification in vivo. To gain insight into this, we have analysed the expression levels and intracellular distribution of MAP2 phosphorylated at this site (MAP2-P), in primary cultures of rat hippocampal neurons at different developmental stages. Western blot analysis of hippocampal neuron protein extracts revealed that the ratio of MAP2-P:MAP2 was 4:1 at early developmental stages and became 1:4 at later developmental stages, suggesting a role of such phosphorylated forms of the protein in neuritogenesis. Consistent with this view, immunofluorescence microscopy analysis showed that the ratio MAP2-P:MAP2 was 2 in the neurite growth cones, sites where net elongation takes place. A higher presence of phosphorylated MAP2 was observed in growth regions with higher levels of microfilaments, which may be related with the growth region stability. Indeed, when growth-cone collapse was induced in hippocampal neurons after cytochalasin D treatment, which depolymerizes microfilaments, the ratio MAP2-P:MAP2 in these growing regions decreased down to 1. Finally, acceleration of neuronal maturation induced by the activation of glutamate-receptors triggered a dramatic decrease in the phosphorylation of MAP2 at the site recognized by antibody 305. From these results we suggest that the phosphorylation of MAP2 at its proline-rich region is an important event during neuritogenesis.
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PMID:Microtubule-associated protein-2 located in growth regions of rat hippocampal neurons is highly phosphorylated at its proline-rich region. 1111 37

Self-assembled structures such as vesicles have generated immense interest in recent decades due to their potential in mimicking biological membranes and in acting as drug-delivery systems. Despite the importance of the interaction between these organized assemblies and the surface of biomaterials, little is known about the mechanism involved. In this study, the interaction between giant proline-rich mussel adhesive protein (MAP) vesicles and the microporous apatite surface was investigated by scanning electron microscopy (SEM). We have found that MAP vesicles incubated on the apatite surface similar to osteoclasts, induce site-specific resorption of the apatite surface. However, in contrast to the osteoclastic resorption, the vesicle-induced resorption process appears to be accompanied by an organic matrix-mediated remineralization process. This results in the formation of a variety of complex three-dimensional site-specific "remodelled zones" on the apatite surface of micrometre scale. The mechanism of the formation of "remodelled zones" is discussed in terms of surface phenomena, such as adsorption and deformation of vesicles, site-specific release of resorptive agents, organic matrix-directed remineralization, and Ca-induced fusion, collapse and reshaping of the vesicles on the apatite surface.
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PMID:Interaction between self-assembled protein vesicles and microporous apatite surface. 1534 47

The tau protein belongs to the category of Intrinsically Disordered Proteins (IDP), which in their native state lack a folded structure and fluctuate between many conformations. In its physiological state, tau helps nucleating and stabilizing the microtubules' (MTs) surfaces in the axons of the neurons. Tau is mainly composed by two domains: (i) the binding domain that tightly bounds the MT surfaces and (ii) the projection domain that exerts a long-range entropic repulsive force and thus provides the proper spacing between adjacent MTs. Tau is also involved in the genesis and in the development of the Alzheimer disease when it detaches from MT surfaces and aggregates in paired helical filaments. Unfortunately, the molecular mechanisms behind these phenomena are still unclear. Temperature variation, rarely considered in biological studies, is here used to provide structural information on tau correlated to its role as an entropic spacer between adjacent MTs surfaces. In this paper, by means of small-angle X-ray scattering and molecular dynamics simulation, we demonstrate that tau undergoes a counterintuitive collapse phenomenon with increasing temperature. A detailed analysis of our results, performed by the Ensemble Optimization Method, shows that the thermal collapse is coupled to the occurrence of a transient long-range contact between a region encompassing the end of the proline-rich domain P2 and the first part of the repeats domain, and the region of the N-terminal domain entailing residues 80-150. Interestingly these two regions involved in the tau temperature collapse belong to the flexible projection domain that acts as an entropic bristle and regulates the MTs' architecture. Our results show that temperature is an important parameter that influences the dynamics of the tau projection domain, and hence its entropic behavior.
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PMID:Continuous thermal collapse of the intrinsically disordered protein tau is driven by its entropic flexible domain. 2289 13

Intrinsically disordered protein tau plays a central role in maintaining neuronal network by stabilizing microtubules in axon. Tau reportedly possesses random coil architecture, which is largely inert to alteration in solution conditions. However, the presence of transient compact conformers and residual structure has been evident from previous reports. Also, during Alzheimer's disease, misfolded tau detaches from microtubule and forms ordered filaments, which is the hallmark of the disease. Despite its fundamental role in neuronal physiology and in pathological cascade of several fatal neurodegenerative diseases, tau conformational dynamics remains poorly understood. In the present study, we have explored the effect of ionic strength, temperature and solvent polarity on tau40 conformational preferences using ion mobility mass spectrometry. Investigation of collision cross section revealed that while low ionic strength, elevated temperature and reduced solvent polarity mostly induced partial collapse in tau40 conformers, higher ionic strength led to an expansion of the molecule. Limited proteolysis identified segments of tau40 projection domain and proline-rich region having high order propensity and a C-terminal region having vulnerability for further expansion at altered solution conditions. The high susceptibility for disorder-to-order transition in the above region of the protein might have crucial implication on its role as microtubule spacers, and in cellular signaling cascade. The conformational adaptation of tau40 did not enhance the heparin-induced aggregation proclivity of the protein. Nevertheless, the observed correlation of electrostatic interaction with fibrillation propensity of tau40 might indicate plausible link between hyperphosphorylation at diseased state with tau conformation and self-assembly.
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PMID:Effect of altered solution conditions on tau conformational dynamics: Plausible implication on order propensity and aggregation. 2963 Sep 71