Nephrocytes are cells functionally analogous to podocytes and proximal tubules of the vertebrate kidney. Drosophila adults lacking nephrocytes or with impaired nephrocytes display defects in heart period, which is longer due to a longer diastolic interval, and rhythmicity. Since nephrocytes regulate the circulating levels of many secreted proteins, this system has been used to identify circulating proteins that impact cardiac function.
Nephrocyte loss or dysfunction can be induced genetically. Animals homozygous for an amorphic mutation of Klf15 lose pericardial nephrocytes and garland cells during early stages of development; adults are completely devoid of nephrocytes. Animals allowed to develop normally until adulthood, and then subjected to Klf15 knockdown, also develop cardiomyopathy. Loss-of-function mutations of the gene Amnionless result in impaired nephrocyte function; a lengthening of the diastolic interval of the heart period is also observed.
The impact of reduced function of the Drosophila gene Rph in nephrocytes or in both cardiomyocytes and nephrocytes has been assessed. Rph encodes an effector of a small GTPase protein implicated in vesicular trafficking. Rph is orthologous to 4 human genes, RPH3A, DOC2B, DOC2A, and RPH3AL; it is most closely related to RPH3A. Knockdown of Rph, effected by RNAi, in both cardiomyocytes and nephrocytes leads to structural and functional changes in the heart that result in a decrease in survival. Knockdown of Rph restricted to the nephrocytes results in cardiac dysfunction that is less severe but still significant.
[updated Aug. 2021 by FlyBase; FBrf0222196]
The protein encoded by RPH3A is thought to be an effector for RAB3A, a small GTP-binding protein that plays a central role in regulated exocytosis and secretion. The RPH3A protein may be involved in neurotransmitter release and synaptic vesicle traffic. [Gene Cards, RPH3A, RAB3A; 2021.08.17]
