NDLI: Calnuc plays a role in dynamic distribution of Gαi but not Gβ subunits and modulates ACTH secretion in AtT-20 neuroendocrine secretory cells

Content Provider	Springer Nature : BioMed Central
Author	Lin, Ping Fischer, Thierry Lavoie, Christine Huang, Haining Farquhar, Marilyn Gist
Abstract	In AtT-20 cells ACTH secretion is regulated by both Ca2+ and G proteins. We previously demonstrated that calnuc, an EF-hand Ca2+ binding protein which regulates Alzheimer's β-amyloid precursor protein (APP) biogenesis, binds both Ca2+ as well as Gα subunits. Here we investigate calnuc's role in G protein-mediated regulation of ACTH secretion in AtT-20 neuroendocrine secretory cells stably overexpressing calnuc-GFP. Similar to endogenous calnuc, calnuc-GFP is mainly found in the Golgi, on the plasma membrane (PM), and associated with regulated secretion granules (RSG). By deconvolution immunofluorescence, calnuc-GFP partially colocalizes with Gαi1/2 and Gαi3 at the PM and on RSG. Cytosolic calnuc(ΔSS)-CFP with the signal sequence deleted also partially colocalizes with RSG and partially cosediments with Gαi1/2 in fractions enriched in RSG. Overexpression of calnuc-GFP specifically increases the distribution of Gαi1/2 on the PM whereas the distribution of Gβ subunits and synaptobrevin 2 (Vamp 2) is unchanged. Overexpression of calnuc-GFP or cytosolic calnuc(ΔSS)-CFP enhances ACTH secretion two-fold triggered by mastoparan or GTPγS but does not significantly affect glycosaminoglycan (GAG) chain secretion along the constitutive pathway or basal secretion of ACTH. Calnuc's facilitating effects on ACTH secretion are decreased after introducing anti-Gαi1/2, Gαi3, Gβ or calnuc IgG into permeabilized cells but not when Gα12 or preimmune IgG is introduced. The results suggest that calnuc binds to Gα subunits on the Golgi and on RSG and that overexpression of calnuc causes redistribution of Gαi subunits to the PM and RSG, indicating that calnuc plays a role in dynamic distribution of only Gα but not Gβ subunits. Thus calnuc may connect G protein signaling and calcium signaling during regulated secretion.
Related Links	https://molecularneurodegeneration.biomedcentral.com/counter/pdf/10.1186/1750-1326-4-15.pdf
Ending Page	16
Page Count	16
Starting Page	1
File Format	HTM / HTML
ISSN	17501326
DOI	10.1186/1750-1326-4-15
Journal	Molecular Neurodegeneration
Issue Number	1
Volume Number	4
Language	English
Publisher	BioMed Central
Publisher Date	2009-03-25
Access Restriction	Open
Subject Keyword	Neurosciences Neurology Molecular Medicine Light Fraction Heavy Fraction ACTH Secretion Golgi Membrane Cyan Fluorescent Protein
Content Type	Text
Resource Type	Article
Subject	Neurology (clinical) Molecular Biology Cellular and Molecular Neuroscience
Journal Impact Factor	15.1/2023
5-Year Journal Impact Factor	16.8/2023

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Calnuc plays a role in dynamic distribution of Gαi but not Gβ subunits and modulates ACTH secretion in AtT-20 neuroendocrine secretory cells

Calnuc plays a role in dynamic distribution of G alpha i but not G beta subunits and modulates ACTH secretion in AtT-20 neuroendocrine secretory cells.

Expression of Rab3D N135I inhibits regulated secretory ACTH in AtT-20 cells (1998)

Constitutive and basal secretion from the endocrine (1991).

Correlation between electrical activity and acth/fl-endorphin secretion in mouse pituitary tumor cells.

Constitutive and basal secretion from the endocrine.

Intracellular and transcellular transport of secretory component and albumin in rat hepatocytes.

A direct inhibitory action of prostaglandins upon ACTH secretion at the late stages of the secretory pathway of AtT-20 cells

Targeting of secretory vesicles to cytoplasmic domains (1988)

Calnuc plays a role in dynamic distribution of Gαi but not Gβ subunits and modulates ACTH secretion in AtT-20 neuroendocrine secretory cells

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Calnuc plays a role in dynamic distribution of Gαi but not Gβ subunits and modulates ACTH secretion in AtT-20 neuroendocrine secretory cells

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Expression of Rab3D N135I inhibits regulated secretory ACTH in AtT-20 cells (1998)

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Calnuc plays a role in dynamic distribution of Gαi but not Gβ subunits and modulates ACTH secretion in AtT-20 neuroendocrine secretory cells