Strathprints Home | Open Access | Browse | Search | User area | Copyright | Help | Library Home | SUPrimo

Palmitoylation and membrane interactions of the neuroprotective chaperone cysteine-string protein

Greaves, Jennifer and Salaun, Christine and Fukata, Yuko and Fukata, Masaki and Chamberlain, Luke H (2008) Palmitoylation and membrane interactions of the neuroprotective chaperone cysteine-string protein. Journal of Biological Chemistry, 283 (36). pp. 25014-25026. ISSN 0021-9258

Full text not available in this repository. (Request a copy from the Strathclyde author)

Abstract

Cysteine-string protein (CSP) is an extensively palmitoylated DnaJ-family chaperone, which exerts an important neuroprotective function. Palmitoylation is required for the intracellular sorting and function of CSP, and thus it is important to understand how this essential modification of CSP is regulated. Recent work identified 23 putative palmitoyl transferases containing a conserved DHHC domain in mammalian cells, and here we show that palmitoylation of CSP is enhanced specifically by co-expression of the Golgi-localized palmitoyl transferases DHHC3, DHHC7, DHHC15, or DHHC17. Indeed, these DHHC proteins promote stable membrane attachment of CSP, which is otherwise cytosolic. An inverse correlation was identified between membrane affinity of unpalmitoylated CSP mutants and subsequent palmitoylation: mutants with an increased membrane affinity localize to the endoplasmic reticulum (ER) and are physically separated from the Golgi-localized DHHC proteins. Palmitoylation of an ER-localized mutant could be rescued by brefeldin A treatment, which promotes the mixing of ER and Golgi membranes. Interestingly though, the palmitoylated mutant remained at the ER following brefeldin A washout and did not traffic to more distal membrane compartments. We propose that CSP has a weak membrane affinity that allows the protein to locate its partner Golgi-localized DHHC proteins directly by membrane "sampling." Mutations that enhance membrane association prevent sampling and lead to accumulation of CSP on cellular membranes such as the ER. The coupling of CSP palmitoylation to Golgi membranes may thus be an important requirement for subsequent sorting.

Item type: Article
ID code: 32489
Keywords: acyltransferases, animals, brefeldin A, cell membrane, endoplasmic reticulum, golgi apparatus, HSP40 heat-shock proteins, humans, lipoylation, membrane proteins, mice, mutation, neuroprotective agents, PC12 cells, protein structure, tertiary, protein synthesis inhibitors, protein transport, rats, Therapeutics. Pharmacology
Subjects: Medicine > Therapeutics. Pharmacology
Department: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
Related URLs:
    Depositing user: Pure Administrator
    Date Deposited: 10 Aug 2011 11:49
    Last modified: 12 Mar 2012 11:30
    URI: http://strathprints.strath.ac.uk/id/eprint/32489

    Actions (login required)

    View Item