Cysteine string protein expression in mammary epithelial cells

Gleave, Terry; Beechey, R. B.; Burgoyne, Robert D.

doi:10.1007/s004240000478

Cited by 6 publications

(4 citation statements)

References 58 publications

(115 reference statements)

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“…CSP was detected in the lysates ( Figure 1G). In epithelial cells, CSP is known to consist of at least two isoforms, depending on the makeup of the C-terminal amino acids: CSP1 (33-37 kD; sometimes referred to as CSPa), which is the most abundant, and CSP2 (26-28 kD) (20,21). NHBE cells appeared to contain the CSP1 isoform based on molecular weight (z 37 kD) as determined by SDS-PAGE.…”

Section: Airway Epithelial Cells Contain Csp1mentioning

confidence: 99%

MARCKS Regulation of Mucin Secretion by Airway Epithelium in Vitro

Park

Fang

Crews

et al. 2008

Am J Respir Cell Mol Biol

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We have reported previously that myristoylated alanine-rich C kinase substrate (MARCKS) is a key regulatory molecule controlling mucin secretion by airway epithelial cells in vitro and in vivo. The results of those studies supported a mechanism whereby MARCKS, upon phosphorylation by protein kinase C (PKC), translocates from plasma membrane to cytoplasm, where its binding to membranes of intracellular mucin granules is a key component of the secretory pathway. It remains unknown how MARCKS is targeted to and/or preferentially attaches to mucin granule membranes. We hypothesized that the chaperone cysteine string protein (CSP) may play an important role in this process. CSP was shown to associate with membranes of intracellular mucin granules in well-differentiated normal human bronchial epithelial (NHBE) cells in vitro, as determined by ultrastructural immunohistochemistry and Western blotting of isolated granule membranes. CSP in these cells complexed with MARCKS, as shown by co-immunoprecipitation. Given reported associations between CSP and a second chaperone, heat shock protein 70 (HSP70), a role for HSP70 in the MARCKS-dependent secretory mechanism also was investigated. HSP70 appeared to form a trimeric complex with MARCKS and CSP associated with mucin granule membranes within airway epithelial cells. Transfection of the HBE1 human bronchial epithelial cell line with siRNAs targeting sequences of MARCKS, CSP, or HSP70 resulted, in each case, in significant knockdown of expression of these proteins and subsequent attenuation of mucin secretion. The results provide the first evidence that CSP and HSP70, and their interactions with MARCKS, are involved in mucin secretion.

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Section: Airway Epithelial Cells Contain Csp1mentioning

confidence: 99%

MARCKS Regulation of Mucin Secretion by Airway Epithelium in Vitro

Park

Fang

Crews

et al. 2008

Am J Respir Cell Mol Biol

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“…A summary of the evidence opposing a CSP regulation of VDCCs as its major function is thus: (i) CSP expression effects on exocytosis are preserved in permeabilized mammalian neuroendocrine cells; (ii) neurotransmission is inhibited downstream of Ca 2+ ‐entry in dCSP mutant neuromuscular junctions; (iii) Ca 2+ ‐currents are normal in dCSP mutant peptidergic nerve terminals; and finally (iv) not all cell types that express CSP also express VDCCs, e.g. (36).…”

Section: The Functions Of Csp At Different Stages Of Regulated Exocytmentioning

confidence: 99%

Tying Everything Together: The Multiple Roles of Cysteine String Protein (CSP) in Regulated Exocytosis

Evans

Morgan

Burgoyne

2003

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In addition to the core vesicle fusion machinery, the SNARE proteins, a large number of regulatory proteins have been implicated in the process of Ca 2+ -dependent exocytosis. How these exocytotic proteins are properly targeted and how their myriad interactions are temporally and spatially coordinated is poorly understood. Cysteine string protein (CSP), a secretory vesicle membrane protein and a member of the dnaJ family of co-chaperones, may assist in performing this function. Through its interaction with the ubiquitous chaperone, Hsc70, it is thought that cysteine string protein targets chaperone complexes to the exocytotic machinery to facilitate the correct folding of polypeptides or to regulate the assembly of protein complexes. Since its discovery, there have been conflicting reports from different systems concerned with whether cysteine string protein exerts its effects on exocytosis either up-or down-stream of Ca 2+ -influx. In this review, we summarize recent experiments that associate cysteine string protein with the regulation of vesicle filling, vesicle docking, Ca 2+ -channels and the SNARE proteins themselves, hence supporting a role for cysteine string protein as a multifunctional secretory co-chaperone. In addition, we provide an update on the mammalian isoforms of cysteine string protein following the recent discovery of two novel cysteine string proteins.

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“…In these organelles, Cgs constitute the main protein component of the intravesicular matrix. Several functions have been proposed for Cgs including a granulogenic action (Mahapatra et al, 2005;Courel et al, 2006), sorting of secretory proteins into the regulated pathway (Gleave et al, 2001), Ca 2ϩ and catecholamine (CA) sequestration (Helle et al, 1985;Videen et al, 1992;Wen et al, 2004), and as a source of bioactive peptides (Winkler et al, 1998;Taupenot et al, 2003). The presence of Cgs-derived active peptides has been linked to the regulation of arterial blood pressure (Mahapatra et al, 2005) or innate immunity (Brekke et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

The Crucial Role of Chromogranins in Storage and Exocytosis Revealed Using Chromaffin Cells from Chromogranin A Null Mouse

Montesinos¹,

Machado²,

Camacho³

et al. 2008

J. Neurosci.

121

142

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Chromogranins (Cgs) are the major soluble proteins of dense-core secretory vesicles. Chromaffin cells from Chga null mice [chromogranin A knock-out (CgA-KO)] exhibited ϳ30% reduction in the content and in the release of catecholamines compared with wild type. This was because of a lower secretion per single exocytotic event, rather than to a lower frequency of exocytotic events. Cell incubation with L-DOPA produced an increase in the vesicular amine content of wild-type, but not CgA-KO vesicles. In contrast, intracellular electrochemistry showed that L-DOPA produced a significantly larger increase in cytosolic amines in CgA-KO cells than in the wild type. These data indicate that the mechanisms for vesicular accumulation in CgA-KO cells were fully saturated. Patch-amperometry recordings showed a delayed initiation of the amperometric signal after vesicle fusion, whereas no changes were observed in vesicle size or fusion pore kinetics despite the smaller amine content. We conclude that intravesicular proteins are highly efficient systems directly implicated in transmitter accumulation and in the control of neurosecretion.

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Cysteine string protein expression in mammary epithelial cells

Cited by 6 publications

References 58 publications

MARCKS Regulation of Mucin Secretion by Airway Epithelium in Vitro

MARCKS Regulation of Mucin Secretion by Airway Epithelium in Vitro

Tying Everything Together: The Multiple Roles of Cysteine String Protein (CSP) in Regulated Exocytosis

The Crucial Role of Chromogranins in Storage and Exocytosis Revealed Using Chromaffin Cells from Chromogranin A Null Mouse

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