Tyrosine plasticity

Tyrosine phosphorylation plays an important role in synaptic transmission and plasticity 430... 

Tyrosine phosphorylation plays an important role in synaptic transmission and plasticity. Evidence for this role is that modulators of PTKs and PTPs have been shown to be intimately involved in these synaptic functions. Among the various modulators of PTKs, neuro-trophins have been extensively studied in this regard and will be our focus in the following discussion (for details of growth factors, see Ch. 27). BDNF and NT-3 have been shown to potentiate both the spontaneous miniature synaptic response and evoked synaptic transmission in Xenopus nerve-muscle cocultures. Neurotrophins have also been reported to augment excitatory synaptic transmission in central synapses. These effects of neurotrophins in the neuromuscular and central synapses are dependent on tyrosine kinase activities since they are inhibited by a tyrosine kinase inhibitor, K-252a. Many effects of neurotrophins on synaptic functions have been attributed to the enhancement of neurotransmitter release BDNF-induced increase in neurotransmitter release is a result of induced elevation in presynaptic cytosolic calcium. Accordingly, a presynaptic calcium-depen-dent phenomenon - paired pulse facilitation - is impaired in mice deficient in BDNF. 

Like many other ligand-gated ion chaimels, the charmel gating properties of the NMDA receptor are regulated by phosphorylation. The NR2 subimit of the receptor contains many Tyr phosphorylation sites in the cytoplasmic region and it has been shown that receptor activity is stimulated by Tyr phosphorylation. Cytoplasmic nonreceptor tyrosine kinases of the Src family are responsible for the Tyr phosphorylation. Thus, a specific association with PSD-95, and thereby mediation of phosphorylation of NR2, has been demonstrated for the Fyn kinase, a member of the Src kinase family (Tezuka et al., 1999). Thus, the nonreceptor tyrosine kinase has an important role in regulation of synaptic activity and plasticity. A model for Fyn association with the NMDA receptor/PSD95 complex is shown in Fig. 16.11. 

Another mechanism of synaptic dysfunction in AD may involve amyloid ft peptide (Aft a 40 to 42 amino acid peptide). A marked increase in Aft levels occurs in brain tissue from AD patients. A ft inhibits glutamatergic neurotransmission and reduces synaptic plasticity (Snyder et al., 2005). Treatment of cortical neuronal cultures with Aft facilitates endocytosis of NMDA receptor. Aft-mediated endo-cytosis of NMDA receptor requires the a-1 nicotinic receptor, protein phosphatase 2B, and the tyrosine phosphatase STEP. Dephosphorylation of the NMDA receptor subunit NR2B at Tyrl472 correlates with receptor endocytosis. The addition of a y-secretase inhibitor not only reduces Aft but also restores surface expression of NMDA receptors, suggesting that A plays an important role in the regulation of NMDA and AMPA receptor trafficking (Snyder et al., 2005 Morishita et al., 2005). 

Conversion of the Microbially Produced Preadhesive to an Adhesive Protein. The polyphenolic protein purified from yeast adheres to a wide variety of surfaces including glass and plastic. The adherence probably results from the presence of many polar residues capable of hydrogen bonding and lysine residues that can form ionic interactions. However, this protein does not generate water-resistant bonds to surfaces nor does it have cohesive strength. For those purposes, it is necessary to convert at least a portion of the tyrosine residues to dopa and permit crosslink formation to occur after surface adhesion is achieved. That is, it is necessary to mimic the natural mussel process in which the dopa form of the polyphenolic protein is applied and then rapidly... 

Purcell, A.L. and Carew, T.J. (2003) Tyrosine kinases, synaptic plasticity and memory insights from vertebrates and invertebrates. Trends Neurosci. 26,625-630. 

Early studies of the plasticity of wool fibers revealed an apparent relationship between sulfur content and plasticity (Ripa and Speakman, 1950, 1951), but this was later shown to be fortuitous (Dry et al., 1952). Differences in plasticity of individual fibers were found to be related to their origin (Dry et al., 1952 Burley and Speakman, 1953), primary follicles producing less plastic fibers than secondary follicles. LeRoux and Speakman (1957) demonstrated a direct relationship between the diametral swelling of fibers in water or formic acid and their rate of creep. They also suggested (LeRoux and Speakman, 1955, 1957) that there is a relationship between the plasticities and the tyrosine contents of individual fibers as determined radiometrically by iodination. It was thought that tyrosine residues contribute to disorder and hence to greater plasticity in the fiber. 

Nadi NS, Head R, Grillo M, Hempstead J, Grannot-Reisfeld N, et al. 1981. Chemical deafferentation of the olfactory bulb Plasticity of the levels of tyrosine hydroxylase, dopamine and norepinephrine. Brain Res 213 365-377. 

Keywords Adenylyl cyclase Aminoalkylindole Anandamide Ca Cannabinoid Cyclic AMP Depolarization suppression of inhibition or excitation Desensitization Endocannabinoid G proteins Ion channels Mitogen activated protein kinases Neurotransmission Nitric oxide Serine/threonine kinases Seven-transmembrane spanning receptors Synaptic plasticity Tyrosine kinases... 

Structural basis of plasticity in protein tyrosine phosphatase IB substrate recognition. Biochemistry 39 8171-8179... 

The phenol structure is widespread in nature as vitamin E, oil of wintergreen, vanillin, the amino acid tyrosine, adrenalin, and tetrahydrocannibinaol (the hallucinogen ingredient of marijuana). Phenol compounds are used as antiseptics and disinfectants, as antioxidants, and to manufacture plastics and aspirin. 

---