Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2009-4-27
pubmed:abstractText
The heat shock protein 70 family members Hsc70 and Hsp70 are known to play a protective role against the onset of experimental pancreatitis, yet their molecular function in acini is unclear. Cysteine string protein (CSP-alpha) is a zymogen granule (ZG) membrane protein characterized by an NH(2)-terminal "J domain" and a central palmitoylated string of cysteine residues. The J domain functions as a cochaperone by modulating the activity of Hsc70/Hsp70 family members. A role for CSP-alpha in regulating digestive enzyme exocytosis from pancreas was investigated by introducing CSP-alpha truncations into isolated acini following their permeabilization with Perfringolysin O. Incubation of acini with CSP-alpha(1-82), containing the J domain, significantly augmented Ca(2+)-stimulated amylase secretion. Effects of CSP-alpha(1-82) were concentration dependent, with a maximum 80% increase occurring at 200 microg/ml of protein. Although CSP-alpha(1-82) had no effects on basal secretion measured in the presence of < or =10 nM free Ca(2+), it did significantly augment GTP-gammaS-induced secretion under basal Ca(2+) conditions by approximately 25%. Mutation of the J domain to abolish its cochaperone activity failed to augment Ca(2+)-stimulated secretion, implicating the CSP-alpha/Hsc70 cochaperone system as a regulatory component of the secretory pathway. CSP-alpha physically associates with vesicle-associated membrane protein 8 (VAMP 8) on ZGs, and the CSP-alpha-VAMP 8 interaction was dependent on amino acids 83-112 of CSP-alpha. Immunofluorescence analysis of acinar lobules or purified ZGs confirmed the CSP-alpha colocalization with VAMP 8. These data establish a role for CSP-alpha in regulating digestive enzyme secretion and suggest that CSP-alpha and Hsc70 modulate specific soluble N-ethylmaleimide-sensitive attachment receptor interactions necessary for exocytosis.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/19282376-10194413, http://linkedlifedata.com/resource/pubmed/commentcorrection/19282376-10430018, http://linkedlifedata.com/resource/pubmed/commentcorrection/19282376-10575024, http://linkedlifedata.com/resource/pubmed/commentcorrection/19282376-10662817, http://linkedlifedata.com/resource/pubmed/commentcorrection/19282376-10872413, http://linkedlifedata.com/resource/pubmed/commentcorrection/19282376-10880051, http://linkedlifedata.com/resource/pubmed/commentcorrection/19282376-11086994, http://linkedlifedata.com/resource/pubmed/commentcorrection/19282376-11148145, http://linkedlifedata.com/resource/pubmed/commentcorrection/19282376-11181949, http://linkedlifedata.com/resource/pubmed/commentcorrection/19282376-11231574, http://linkedlifedata.com/resource/pubmed/commentcorrection/19282376-11384973, http://linkedlifedata.com/resource/pubmed/commentcorrection/19282376-11478872, http://linkedlifedata.com/resource/pubmed/commentcorrection/19282376-11580898, http://linkedlifedata.com/resource/pubmed/commentcorrection/19282376-11790807, http://linkedlifedata.com/resource/pubmed/commentcorrection/19282376-11812646, http://linkedlifedata.com/resource/pubmed/commentcorrection/19282376-11931641, http://linkedlifedata.com/resource/pubmed/commentcorrection/19282376-12737809, http://linkedlifedata.com/resource/pubmed/commentcorrection/19282376-12783986, http://linkedlifedata.com/resource/pubmed/commentcorrection/19282376-1326297, http://linkedlifedata.com/resource/pubmed/commentcorrection/19282376-14977633, http://linkedlifedata.com/resource/pubmed/commentcorrection/19282376-15007177, http://linkedlifedata.com/resource/pubmed/commentcorrection/19282376-15091340, http://linkedlifedata.com/resource/pubmed/commentcorrection/19282376-15363411, http://linkedlifedata.com/resource/pubmed/commentcorrection/19282376-15610015, http://linkedlifedata.com/resource/pubmed/commentcorrection/19282376-15972823, http://linkedlifedata.com/resource/pubmed/commentcorrection/19282376-16055447, http://linkedlifedata.com/resource/pubmed/commentcorrection/19282376-16258366, http://linkedlifedata.com/resource/pubmed/commentcorrection/19282376-16269331, http://linkedlifedata.com/resource/pubmed/commentcorrection/19282376-16477021, http://linkedlifedata.com/resource/pubmed/commentcorrection/19282376-16842158, http://linkedlifedata.com/resource/pubmed/commentcorrection/19282376-16875662, http://linkedlifedata.com/resource/pubmed/commentcorrection/19282376-17113038, http://linkedlifedata.com/resource/pubmed/commentcorrection/19282376-17272274, http://linkedlifedata.com/resource/pubmed/commentcorrection/19282376-18438606, http://linkedlifedata.com/resource/pubmed/commentcorrection/19282376-18535671, http://linkedlifedata.com/resource/pubmed/commentcorrection/19282376-18595009, http://linkedlifedata.com/resource/pubmed/commentcorrection/19282376-7666205, http://linkedlifedata.com/resource/pubmed/commentcorrection/19282376-7906056, http://linkedlifedata.com/resource/pubmed/commentcorrection/19282376-8132647, http://linkedlifedata.com/resource/pubmed/commentcorrection/19282376-8310297, http://linkedlifedata.com/resource/pubmed/commentcorrection/19282376-8606785, http://linkedlifedata.com/resource/pubmed/commentcorrection/19282376-8631751, http://linkedlifedata.com/resource/pubmed/commentcorrection/19282376-8824236, http://linkedlifedata.com/resource/pubmed/commentcorrection/19282376-8898648, http://linkedlifedata.com/resource/pubmed/commentcorrection/19282376-8940165, http://linkedlifedata.com/resource/pubmed/commentcorrection/19282376-8970162, http://linkedlifedata.com/resource/pubmed/commentcorrection/19282376-9148760, http://linkedlifedata.com/resource/pubmed/commentcorrection/19282376-9188511, http://linkedlifedata.com/resource/pubmed/commentcorrection/19282376-9693380, http://linkedlifedata.com/resource/pubmed/commentcorrection/19282376-9724640, http://linkedlifedata.com/resource/pubmed/commentcorrection/19282376-9824305
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Calcium, http://linkedlifedata.com/resource/pubmed/chemical/Enzymes, http://linkedlifedata.com/resource/pubmed/chemical/Guanosine 5'-O-(3-Thiotriphosphate), http://linkedlifedata.com/resource/pubmed/chemical/HSC70 Heat-Shock Proteins, http://linkedlifedata.com/resource/pubmed/chemical/HSP40 Heat-Shock Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Hspa8 protein, rat, http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments, http://linkedlifedata.com/resource/pubmed/chemical/R-SNARE Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins, http://linkedlifedata.com/resource/pubmed/chemical/SNARE Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Vamp8 protein, rat, http://linkedlifedata.com/resource/pubmed/chemical/cysteine string protein
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0193-1857
pubmed:author
pubmed:issnType
Print
pubmed:volume
296
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
G1030-9
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