Are the renin-containing granules of juxtaglomerular epithelioid cells modified lysosomes?

Abstract

Mature secretory granules of epithelioid cells--the so-called renin granules--exhibit certain properties, which in this particular combination are expressed only by lysosomes: Renin granules have autophagic capabilities; they react to the application of lipidosis-inducing, lysosomotropic substances by the gradual accumulation of polar lipids; all secretory granules of epithelioid cells contain acid phosphatase until maturity; and exogenous tracers reach renin granules without labeling the Golgi complex. Several functional implications can therefore be considered. Hydrolytic enzymes, constitutive elements of the granule matrix, might either cleave inactive prorenin to yield active renin within the granules or, by unspecific hydrolysis of renin, participate in the regulation of the overall quantity of secretory product. Autophagic phenomena, the involvement of renin granules in the traffic of exogenous tracers, and the build-up of polar lipids following experimental interference with lipid catabolism indicate a large turnover of membrane material in renin granules. They also suggest that cytoplasmic and extracellular fluid gains access to the granule content and may thus be involved there in the regulation of biochemical reactions by changing the intragranular milieu or via signal molecules. In addition to the lysosome-like properties of epithelioid cell secretory granules, the secretory product, renin, as a carboxyl protease, is structurally related to other acidic proteases. In the case of cathepsin D, even functional similarities exist.

Ultrastructural Juxtaglomerular Cell Changes in Normotensive Rats Treated with Quinapril, an Inhibitor of Angiotensin-Converting Enzyme

“…Matrix alterations indicative of autophagy and excessive membrane turnover included invaginations of the granule limiting membrane and vesicular to concentric lamellar inclusions in granules unassociated with plasma membranes (33). Double-membrane bound vacuoles containing granular to flocculent densities, as noted in our study, were also reported to be a consequence of autophagic activity resulting in granule turnover or a result of cytoplasmic herniation and sequestration (45).…”

“…This phenomenon has been reported to occur in JG cells primarily under conditions of decreasing stimulation and results in formation of large granules with flocculent to rarefied matrices (46). However, autophagy of renin granules has also occurred under experimental conditions of acute JG cell stimulation (45). Matrix alterations indicative of autophagy and excessive membrane turnover included invaginations of the granule limiting membrane and vesicular to concentric lamellar inclusions in granules unassociated with plasma membranes (33).…”

Angiotensinogen, Prorenin, and Renin Are Co-localized in the Secretory Granules of All Glandular Cells of the Rat Anterior Pituitary: An Immunoultrastructural Study

“…Renin is also present in ill-defined structures, sometimes containing hormones but with ultrastructural features reminiscent of lysosomes, which have not been previously described in the literature. This would be consistent with the lysosomal nature of some granulations in rat gonadotropes (Tougard et al 1974), which has also been pos-tulated for lactotropes (Saint-André et al 1989) and for renin-secreting cells in the kidney (Taugner et al 1985;Hackenthal et al 1990;Reudelhuber et al 1993). Many authors have reported that gonadotropes also contain AII (Steele et al 1982;Deschepper et al 1986a;Naruse et al 1986;Ganong et al 1989;Thomas and Sernia 1990;Sernia et al 1997), and it is possible that AGT is processed to AII in these cells.…”

Aliskiren Accumulates in Renin Secretory Granules and Binds Plasma Prorenin

“…Thus, apparently, aliskiren is taken up by HMC-1 cells and reaches renin granules. Indeed, it has been suggested in both mast cells 24 and JG cells 25 that early secretory granules have the ability to take up extracellular substances, delivered through retrograde transport via early/ recycling endosomes and surcompassing the Golgi network. 14 This is perhaps not surprising considering that the renin granules originate as lysosomes.…”