Membrane Topology and Intracellular Processing of Cyclin M2 (CNNM2)

Abstract

Background: Mutations in CNNM2 cause severe dominant hypomagnesemia. Results: Structure of CNNM2 consists of an extracellular N terminus and intracellular C terminus containing CBS domains, which are affected by the identified mutations. Conclusion: CNNM2 is intensively processed before being expressed in its final structure at the plasma membrane. Significance: CNNM2 structure analysis will aid to elucidate CNNM2 function in renal magnesium transport.

Identification and lateral membrane localization of cyclin M3, likely to be involved in renal Mg2+handling in seawater fish

“…Specific signals for the Cnnm3 monomer (ϳ85 kDa) and potential dimer (ϳ180 kDa) were detected by anti-Cnnm3 or anti-FLAG antibodies. A similar pattern was observed in the Western blot analysis of mouse Cnnm2 (12). The calculated molecular masses of anti-FLAG preimmune C n n m 3 C n n m 3 -F L A G U n t r a n s f e c t e d C n n m 3 C n n m 3 -F L A G U n t r a n s f e c t e d C n n m 3 C n n m 3 -F L A G U n t r a n s f e c t e d kDa Cnnm3 and FLAG-tagged Cnnm3 are 83 and 87 kDa, respectively.…”

“…In Saccharomyces cerevisiae, MAM3 encodes a homolog of the Cnnm family whose expression levels directly correlate with the degree of Mn toxicity (47). Mammalian Cnnm2 is a plasma membrane protein comprising the following: an N-terminal signal peptide (cleaved by signal peptidases); an extracellular NH 2 terminus; three transmembrane domains; and an intracellular COOH terminus containing two cystathionine ␤-synthase (CBS) domains, a cyclin box motif, and a cyclic nucleotide (cNMP)-binding domain (12,44,45 (19).…”

PRL2 links magnesium flux and sex-dependent circadian metabolic rhythms

“…Primers for Cnnm family genes (Cnnm2-1, Cnnm2-2, Cnnm3-1, Cnnm3-2, and Cnnm4) were described in ref. 58. For assessment of metabolic gene expression, 1 μg of total RNA from BAT was reverse transcribed using the iScript cDNA synthesis kit (Bio-Rad) following the manufacturers recommendations.…”

Distal Convoluted Tubule

“…With regards to basolateral Mg 21 transport, a mechanism exists for the reclamation of magnesium back into the peritubular fluid and bloodstream; however, the precise molecular identities of these transport processes remain obscure. One putative candidate is cyclin M 2 (ancient conserved domain-containing protein 2), a distal nephron-expressed basolateral membrane protein that has been described by some as an Mg 21 /metal ion transporter (107) and others as a magnesium sensor (108,109). Another candidate is the basolateral magnesium transporter SLC41A1, which is localized to the DCT.…”