Protein Phosphorylation and Neuronal Function

Browning, Michael; Huganir, Richard L.; Greengard, Paul

doi:10.1111/j.1471-4159.1985.tb05468.x

Cited by 261 publications

(100 citation statements)

References 129 publications

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“…Biological activities of the purified mPSDp. The change (7,8,38). For example, Ca2+/CaM-dependent phosphorylation of the mPSDp may alter the molecular conformation leading to changes in PSD shape and synaptic spine morphology with altered conductance (1, 7).…”

Section: Discussionmentioning

confidence: 99%

“…Cerebral cortical or hippocampal PSDs contain a predominant protein, the major PSD protein (mPSDp), that binds calmodulin (CaM) in the presence of Ca2+ (2) and appears to be an autophosphorylatable Ca2+/CaM-dependent protein kinase (3)(4)(5). These unique activities are of critical functional significance since Ca2+ influx is a key step in memory formation (6) and since protein phosphorylation is central to signal transduction (7)(8)(9). Indeed, by monitoring the mPSDp, we have previously found that impulse activity regulates synaptic molecular architecture in the developing and mature sympathetic superior cervical ganglion (10)(11)(12).…”

mentioning

confidence: 99%

See 1 more Smart Citation

On the identity of the major postsynaptic density protein.

Wu¹,

Huang²,

Adler³

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

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Increasing evidence suggests that the postsynaptic density (PSD) plays a critical role in synaptic communication and plasticity. The major PSD protein (mPSDp), a calcium/calmodulin-dependent protein kinase, appears to be central to PSD function. The mPSDp has long been considered identical to the a subunit of the soluble calmodulin kinase II (a-CKII). However, mPSDp and a-CKII do differ in solubility and antigenicity, raising the possibility that the two proteins are distinct. To further derme the relationship between the two proteins, we purified the mPSDp to homogeneity from adult rat cerebral cortex and compared the proteins. In contrast to a-CKII, the purified mPSDp was insoluble in high concentrations of salt, various detergents, chelators of divalent cations, and the strong denaturant guanidine hydrochloride. The pI value of the mPSDp was 6.2, whereas that of a-CKII was 6.7-7.2. The purified mPSDp bound calmodulin in the presence of Ca2' and was autophosphorylated in a Ca2+/calmodulin-dependent manner. Polyclonal antiserum raised against mPSDp (anti-mPSDp) recognized purified mPSDp or mPSDp in synaptic membrane, indicating immunologic specificity among the synaptic proteins. Anti-mPSDp did not recognize a-CKII, whereas anti-a-CKII antibodies reacted only weakly with mPSDp, suggesting that the proteins are distinct but structurally similar. Moreover, sequence analysis of protease V8-digested polypeptides revealed that there was at least an 8-amino acid sequence, MLKVPNIS, that is not present in a-CKII. Finally, HPLC analysis of V8-digested fragments of mPSDp and a-CKII in parallel revealed dissimilar peptide patterns. Thus our observations suggest that mPSDp and a-CKII are similar but not identical. The unique physicochemical and structural properties of the mPSDp may provide insights into molecular mechanisms mediating synaptic plasticity.Numerous studies suggest that the postsynaptic density (PSD), a proteinaceous disc-shaped structure attached to the postsynaptic membrane of chemical synapses, plays a critical role in synaptic communication and plasticity (for review, see ref. 1). Remarkably, however, only few proteins in the PSD have been characterized biochemically. Cerebral cortical or hippocampal PSDs contain a predominant protein, the major PSD protein (mPSDp), that binds calmodulin (CaM) in the presence of Ca2+ (2) and appears to be an autophosphorylatable Ca2+/CaM-dependent protein kinase (3-5). These unique activities are of critical functional significance since Ca2+ influx is a key step in memory formation (6) and since protein phosphorylation is central to signal transduction (7-9). Indeed, by monitoring the mPSDp, we have previously found that impulse activity regulates synaptic molecular architecture in the developing and mature sympathetic superior cervical ganglion (10)(11)(12). Moreover, the synaptic molecule mPSDp is similarly regulated in the adult rat hippocampus (12).Despite its potential functional significance, the identity of the mPSDp and its relationship to the soluble ty...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

On the identity of the major postsynaptic density protein.

Wu¹,

Huang²,

Adler³

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

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show abstract

“…In the central nervous system (CNS), protein kinases play a key role in the postreceptor processing of extracellular signals by phosphorylating specific protein substrates [1]. The role played by phosphorylation of individual proteins in these processes has been mainly inferred from in vitro experiments measuring their degree of phosphorylation by procedures involving back-titration to label residual phosphorylatable sites by means of phosphate incorporation from 32p-labelled ATP [1].…”

Section: Introductionmentioning

confidence: 99%

Determination of the endogenous phosphorylation state of B‐50/GAP‐43 and neurogranin in different brain regions by electrospray mass spectrometry

Luca

Pastorino

Raverdino³

et al. 1996

FEBS Letters

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“…These intracellular regulatory molecules affect many physiological processes by mechanisms which often involve covalent phosphorylation of appropriate rate-limiting enzymes, ion channels or other proteins [1,2]. Three multifunctional protein kinases are thought to mediate many of these phosphorylation reactions, namely cyclic AMP-dependent protein kinase (cAMP-kinase), calcium/phospholipid-dependent protein kinase (protein kinase C) and calcium/calmodulin-dependent protein kinase II (CaM-kinase II).…”

Section: Introductionmentioning

confidence: 99%