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A New View of Macula Densa Cell Biology
Author(s) -
Shroff Urvi Nikhil,
Perin Laura,
PetiPeterdi Janos
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.701.8
Subject(s) - macula densa , microbiology and biotechnology , cell cycle , exocytosis , biology , rhoptry , organelle , chemistry , tubuloglomerular feedback , endoreduplication , cell , biochemistry , kidney , secretion , genetics , immunology , apicomplexa , renin–angiotensin system , malaria , blood pressure , plasmodium falciparum , endocrinology
Macula densa (MD) cells of the juxtaglomerular apparatus (JGA) perform important, well‐characterized physiological regulatory functions including tubuloglomerular feedback‐mediated control of glomerular hemodynamics and renin release. Established chemical mediators synthesized and released from MD cells include ATP, adenosine, PGE2, and NO that are of non‐protein nature. However, the unique features of MD cell organelles, the apically located giant nuclei and the robust size of protein synthesis organelles at the cell base suggest that the MD is a massive protein factory. The present study aimed to characterize the basic MD cell biological processes and their regulatory mechanisms. Immunofluorescence localization of the key molecular players in DNA synthesis, cell cycle regulation, protein synthesis, processing, and vesicular release was performed in fixed mouse and human kidney sections. The high level and MD‐specific expression of the key cell cycle regulators Geminin and Wee1 suggested that MD cells are in cell cycle arrest in the G2/M phase. Staining for γ–tubulin revealed multiple centrosomes in some MD cells suggesting DNA endoreduplication (endocycling) and multiploidy. The robust and MD‐specific labeling of secreted angiogenic peptides (Ccn1, Pappa‐2, Gdf15) was localized in numerous small intracellular vesicles, suggesting the high rate of synthesis of these proteins and their release. The high level of MD‐specific expression of unique elements of the actomyosin motor complex (Myh10, Ablim1, Dctn2, Gsn) was also consistent with the presence of a well‐controlled vesicular release (exocytosis) machinery. In summary, MD cells have a unique cell biology and genetic program to power a robust synthetic and secretion machinery of various novel MD‐specific proteins that likely perform important functions in renal tubulo‐interstitial, vascular, and glomerular tissue remodeling. Support or Funding Information NIH R01 64324 , AHA, ADA