Chromogranins A and B as Regulators of Vesicle Cargo and Exocytosis

Abstract

Chromogranins (Cgs) are acidic proteins that have been implicated in several physiological processes such as vesicle sorting, the production of bioactive peptides and the accumulation of soluble species inside large dense core vesicles (LDCV). They constitute the main protein component in the vesicular matrix of LDCV. This latter characteristic of Cgs accounts for the ability of vesicles to concentrate catecholamines and Ca(2+). It is likely that Cgs are behind the delay in the neurotransmitter exit towards the extracellular milieu after vesicle fusion, due to their low affinity and high capacity to bind solutes present inside LDCV. The recent availability of mouse strains lacking Cgs, combined with the arrival of several techniques for the direct monitoring of exocytosis, have helped to expand our knowledge about the mechanisms used by granins to concentrate catecholamines and Ca(2+) in LDCV, and how they affect the kinetics of exocytosis. We will discuss the roles of Cgs A and B in maintaining the intravesicular environment of secretory vesicles and in exocytosis, bringing together the most recent findings from adrenal chromaffin cells.

Stress Triggered Changes in Expression of Genes for Neurosecretory Granules in Adrenal Medulla

“…The chromogranins are acidic proteins and are the most abundant components of secretory vesicles in the chromaffin cells (reviewed in Machado et al 2010;Bartolomucci et al 2003). The chromogranins bind catecholamines and calcium with high capacity and low affinity (Westermann et al 1988;Videen et al 1992).…”

Striatal dopamine neurotransmission: Regulation of release and uptake

“…Granins are found in endocrine and neuroendocrine cells from which they are co-released with monoamines during exocytosis [122,123]. In addition to regulating vesicular levels of transmitters, these proteins (or their proteolytic cleavage products) are implicated in dense-core vesicle formation, vesicular sequestration of Ca 2+ and modulation of exocytosis [122–125]. …”

Excitatory and Inhibitory Neurons in the Hippocampus Exhibit Molecularly Distinct Large Dense Core Vesicles

“…To identify the molecular composition of secretory vesicles in different hippocampal interneuron subtypes, we started by characterizing the expression pattern of canonical LDCV markers CAPS-1 and chromogranin B (Speidel et al, 2003; Machado et al, 2010). According to previous work in primary cultured neurons (Farina et al, 2015), immunohistofluorescence analysis in adult mouse slices revealed high levels of CAPS-1 (Supplemental Figure 4) supporting the notion that this protein is associated with neuronal LDCVs.…”

“…Thus, the chromogranin family (a.k.a. secretogranins) and CAPS have been found in both endocrine and neuronal tissue (Speidel et al, 2003; Machado et al, 2010; Bartolomucci et al, 2011). These findings pointed to the notion that despite the striking diversity of cargo, neuronal secretory vesicles may exhibit a fairly homogenous molecular composition.…”

“…Despite the remarkable variability of their cargo, LDCVs and MDCVs have been considered a molecularly homogenous population constituted by common integral proteins which can be found in both neuroendocrine and nerve cells. This is the case of the calcium-activator proteins for secretion (CAPS) and the chromogranin family (Speidel et al, 2003; Machado et al, 2010; Bartolomucci et al, 2011). Chromogranin B (ChB, a.k.a.…”