Disease relevance of Csp

• The deduced amino-acid (aa) sequence shows strong similarities with Ip peptides from Escherichia coli, yeasts, plants and mammals, with 100% aa identity around the three Cys clusters which form the non-heme iron-sulfur centers [1].
• We have found that the previously identified Cys-rich central region contains multiple novel zinc finger motifs which are also present in the Polycomb-like protein and RBP2, a retinoblastoma binding protein [2].

Psychiatry related information on Csp

• Csp mutants that could generate patterned motor activity had slower, poorly coordinated rhythms with altered temperature sensitivity [3].

High impact information on Csp

• We suggest that Hsc4 and CSP cooperatively augment the probability of release by increasing the Ca(2+) sensitivity of vesicle fusion [4].
• The predicted odd protein of 392 amino acids is highly basic and contains four tandem Cys-Cys/His-His zinc finger repeats, consistent with a presumed function for odd as a DNA binding protein and transcriptional regulator [5].
• Here we show that the serine residues flanking the C-terminal Cys residues of Drosophila TrxRs are responsible for activating the cysteines to match the catalytic efficiency of a selenocysteine-cysteine pair as in mammalian TrxR, obviating the need for selenium [6].
• The amino acid sequence (2547 residues) of the complete open reading frame of the X gene has 44% identity and 88% similarity to the Drosophila sequence and contains the conserved Cys and His domains characteristic of deubiquitinating enzymes, suggesting its biochemical function may be the hydrolysis of ubiquitin from protein-ubiquitin conjugates [7].
• Increased Ca(2+) signals coupled with reduced release suggest a direct function of CSP in exocytosis downstream from Ca(2+) entry [8].

Biological context of Csp

• In addition, other studies have directly implicated Csp in regulated exocytosis in mammalian neuroendocrine and endocrine cell types, and its distribution suggests a general role in regulated exocytosis [9].
• The genome sequences of Caenorhabditis elegans and Drosophila melanogaster reveal a diversity of cysteine-loop ligand-gated ion channels (Cys-loop LGICs) not found in vertebrates [10].
• The 32 and 34 kD brain proteins that presumably are localized predominantly in synaptic terminals of photoreceptors and most if not all neurons may correspond to two variant cysteine-string proteins as they are of similar molecular weight and share an antigenic binding site for MAB ab49 [11].
• Previous work indicated that the temperature-dependent block of synaptic transmission in cysteine string protein (csp) mutants of Drosophila was attributable to a failure of nerve impulses to trigger transmitter release [12].
• Amino acid substitutions at this Cys position in the cardiac alpha1 subunit show that the size of the side chain, rather than its ability to form disulfide bonds, affects channel activation [13].

Anatomical context of Csp

• Cysteine-string protein (Csp) is a major synaptic vesicle and secretory granule protein first discovered in Drosophila and Torpedo [9].
• Collectively, these data suggest multiple functions for CSP at synaptic terminals [8].
• A monoclonal antibody MAB ab49 from a hybridoma library screened for immunohistochemical staining in the adult nervous system of Drosophila melanogaster was found to selectively bind to all neuropil regions and to synaptic boutons of motor neurons [11].
• Our studies reveal that the spider venom toxin alpha-latrotoxin can trigger a sustained discharge of quanta at neuromuscular junctions of csp mutant larvae at nonpermissive temperature [12].
• This supports the hypothesis that CSP links synaptic vesicles to calcium secretion coupling [14].

Associations of Csp with chemical compounds

• Likewise, 4-aminopyridine, which augments transmitter release at permissive temperature in csp mutants, fails to reverse the inhibition of impulse-evoked transmitter release at elevated temperature [12].
• No intermediate with an NH2-terminal Cys or Met could be demonstrated [15].
• In contrast, the Cys homolog of Drosophila melanogaster exhibits a clear preference for Trx, the net forward rate constant, k'(+2), for reduction by Trx being 1.5x10(6) M(-1) s(-1), but only 5.4 M(-1) s(-1) for glutathione [16].
• Virtually all BIRs contain three Cys and a His that bind zinc, a Gly in a tight turn, and an Arg [17].
• Classic performic acid oxidation modifies three residues, Cys to CysO(3), Met to MetO(2), and Trp to TrpO(2) [18].

References