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Rab3a controls exocytosis in cholecystokinin-secreting cells
J C Gevrey1, S Laurent, J C Saurin
1INSERM Unité 45, Hôpital Edouard Herriot, Lyon, France.
FEBS Letters
|August 22, 2001
Summary
Intestinal endocrine cells express rab3A and rab3D proteins. The GTP-bound form of rab3A negatively modulates cholecystokinin secretion in STC-1 cells, impacting human growth hormone release.
Area of Science:
- Molecular Biology
- Cell Biology
- Endocrinology
Background:
- Rab GTPases are crucial regulators of intracellular membrane trafficking.
- Specific Rab isoforms, such as rab3A and rab3D, are implicated in regulated exocytosis.
- Enteroendocrine cells secrete hormones like cholecystokinin (CCK) in response to stimuli.
Purpose of the Study:
- To investigate the expression of rab3 isoforms in intestinal enteroendocrine cell lines.
- To determine the functional role of rab3A and rab3D in regulating CCK secretion.
- To elucidate the specific contribution of GTP-bound rab3A to secretory responses.
Main Methods:
- Analysis of rab3A, rab3B, rab3C, and rab3D expression in STC-1 and GLUTag cell lines.
- Transient co-transfection of STC-1 cells with human growth hormone as a reporter.
- Overexpression of GTPase-deficient rab3A (rab3AQ81L) and rab3D (rab3DQ81L) mutants.
Main Results:
- Rab3A and rab3D were expressed in STC-1 and GLUTag cells; rab3B was undetectable, and rab3C showed low expression.
- Overexpression of rab3AQ81L, but not rab3DQ81L, significantly reduced human growth hormone secretory responses to agonists in STC-1 cells.
- These findings suggest a specific inhibitory role for GTP-bound rab3A in CCK secretion.
Conclusions:
- Intestinal endocrine cell lines STC-1 and GLUTag express rab3A and rab3D isoforms.
- The GTP-bound form of rab3A acts as a negative modulator of cholecystokinin secretion.
- Rab3A plays a specific role in the regulation of CCK release from enteroendocrine cells.