Cytochrome b561 can be detected in many neuroendocrine tissues using a specific monoclonal antibody

Avivi

Proc. Natl. Acad. Sci. U.S.A.

et al. 2008

Although many genes have been shown to play essential roles in learning and memory, the precise molecular and cellular mechanisms underlying these processes remain to be fully elucidated. Here, we present the molecular and behavioral characterization of the Drosophila memory mutant nemy. We provide multiple lines of evidence to show that nemy arises from a mutation in a Drosophila homologue of cytochrome B561. nemy is predominantly expressed in neuroendocrine neurons in the larval brain, and in mushroom bodies and antennal lobes in the adult brain, where it is partially coexpressed with peptidyl ␣-hydroxylating monooxygenase (PHM), an enzyme required for peptide amidation. Cytochrome b561 was found to be a requisite cofactor for PHM activity and we found that the levels of amidated peptides were reduced in nemy mutants. Moreover, we found that knockdown of PHM gave rise to defects in memory retention. Altogether, the data are consistent with a model whereby cytochrome B561-mediated electron transport plays a role in memory formation by regulating intravesicular PHM activity and the formation of amidated neuropeptides.

Section: Discussionmentioning

confidence: 72%

nemy encodes a cytochrome b561 that is required for Drosophila learning and memory

Avivi

Proc. Natl. Acad. Sci. U.S.A.

et al. 2008

Biochimica et Biophysica Acta (BBA) - General Subjects

“…The organ distribution pattern of LCytb is very different from those of two other Cyts b561, CGCytb and Dcytb. CGCytb was mainly found in the adrenal medulla, the pituitary gland and other neuroendocrine tissues [21][22][23], while Dcytb was mainly found in the duodenum and was possibly present in spleen, liver, brain, leucocytes, erythrocytes and neutrophils [6,24,25].…”

Section: Discussionmentioning

confidence: 99%

An ascorbate-reducible cytochrome b561 is localized in macrophage lysosomes

Zhang

Bérczi

et al. 2006

Cytochromes b561 (Cyts b561) are a family of intrinsic membrane proteins involved in ascorbate-mediated transmembrane electron transport. The chromaffin granule Cyt b561 (CGCytb) is believed to transport electrons donated by extravesicular ascorbate (ASC) across the membrane to intravesicular monodehydroascorbate (MDA) supporting catecholamine synthesis in neuroendocrine tissues. Another isoform, the duodenal Cyt b561 (Dcytb), was reported to have ferric reductase activity, possibly facilitating intestinal iron uptake. Herein, a new Cyt b561 homologue, LCytb (for lysosomal Cytb561) was found expressed in the late endosomal-lysosomal membrane. LCytb shared high sequence similarity with CGCytb (45% identity) and Dcytb (42% identity). Moreover, four heme-coordinating His residues, and putative ASC and MDA binding sites were highly conserved. Recombinant LCytb exhibited an ASC-reducible b-type Cyt absorbance spectrum with α-band maximum at 561 nm in the spectrum of the reduced protein. Northern blots and Western blots revealed that LCytb was predominantly expressed in lung, spleen, thymus, testis and placenta. In situ hybridization and immunofluorescence studies further demonstrated that the protein was expressed in the alveolar macrophages of the lung, in the white pulp of the spleen, widespread in the thymus, and in the Sertoli cells of the testis. Sequence analysis indicated the presence of a (DE)XXXL(LI)-type signal in the C-terminal of the protein, predicting a late endosomal-lysosomal subcellular localization. This localization was confirmed by double labeling experiments in RAW264.7 and 293 cells, stably transfected with LCytb.

Antioxidants & Redox Signaling

“…CGCytb/CYB561A1 was first identified in catecholaminesynthesizing (chromaffin) vesicles, and was, consistently, demonstrated in various neuroendocrine tissues (53). It is now clear that plant and animal CYB561s occur in a wide range of organs, tissues, and cell types.…”

Section: Tissue-and Subcellular-distributionmentioning

confidence: 99%

Cytochromesb561: Ascorbate-Mediated Trans-Membrane Electron Transport

Asard

Barbaro

Trost

et al. 2013

Significance: Cytochromes b561 (CYB561s) constitute a family of trans-membrane (TM), di-heme proteins, occurring in a variety of organs and cell types, in plants and animals, and using ascorbate (ASC) as an electron donor. CYB561s function as monodehydroascorbate reductase, regenerating ASC, and as Fe 3+ -reductases, providing reduced iron for TM transport. A CYB561-core domain is also associated with dopamine bmonooxygenase redox domains (DOMON) in ubiquitous CYBDOM proteins. In plants, CYBDOMs form large protein families. Physiological functions supported by CYB561s and CYBDOMs include stress defense, cell wall modifications, iron metabolism, tumor suppression, and various neurological processes, including memory retention. CYB561s, therefore, significantly broaden our view on the physiological roles of ASC. Recent Advances: The ubiquitous nature of CYB561s is only recently being recognized. Significant advances have been made through the study of recombinant CYB561s, revealing structural and functional properties of a unique ''two-heme four-helix'' protein configuration. In addition, the DOMON domains of CYBDOMs are suggested to contain another heme b. Critical Issues: New CYB561 proteins are still being identified, and there is a need to provide an insight and overview on the various roles of these proteins and their structural properties. Future Directions: Mutant studies will reveal in greater detail the mechanisms by which CYB561s and CYBDOMs participate in cell metabolism in plants and animals. Moreover, the availability of efficient heterologous expression systems should allow protein crystallization, more detailed (atomic-level) structural information, and insights into the intramolecular mechanism of electron transport.