Disease relevance of ATP2B1

• The DNA probe for Northern analysis was obtained by reverse transcription and PCR with intestinal poly(A)+ RNA, using two 20-mer oligonucleotide primers homologous to the 3' coding region of the human teratoma PMCA [1].
• The monoclonal antibody 5F10 was used to examine the distribution of PMCA in chick Edinger-Westphal neurons, a population of cholinergic preganglionic neurons whose cells bodies reside in the Edinger-Westphal nucleus in the brainstem and whose axons form synaptic terminals on parasympathetic neurons in the ciliary ganglion [2].

High impact information on ATP2B1

• The effect of vitamin D and other variables on the synthesis of the chicken intestinal plasma membrane calcium pump (PMCA) mRNA was assessed [1].
• These results indicate that vitamin D and specific variables that affect calcium absorption through the vitamin D-endocrine system increase intestinal PMCA gene expression [1].
• Northern analysis with the chicken PMCA DNA indicated that repletion of vitamin D-deficient chickens with vitamin D increased PMCA mRNAs in the duodenum, jejunum, ileum, and colon [1].
• We propose that the inability of CaM to fully activate the PMCA after methionine oxidation originates in a reduced helical propensity for M144 and M145, and results primarily from a global rearrangement of the tertiary structure of the C-terminal globular domain that substantially alters the interaction of this domain with the PMCA [3].
• The functional expression and distribution of intracellular ATPase (sarco(endo)plasmic reticulum Ca(2+)-ATPase: SERCA) and plasma membrane Ca(2+)-ATPase (PMCA) was analyzed in the developing chick cerebellum [4].

Biological context of ATP2B1

• These results suggest that oxidative modification of PMCA reduced the propensity of the autoinhibitory domain to dissociate from binding sites near the catalytic core of the enzyme with bound nucleotide upon CaM stimulation in the presence of Ca(2+) [5].
• The C-terminus of calmodulin (CaM) functions as a sensor of oxidative stress, with oxidation of methionine 144 and 145 inducing a nonproductive association of the oxidized CaM with the plasma membrane Ca(2+)-ATPase (PMCA) and other target proteins to downregulate cellular metabolism [3].
• The expression pattern and spatial distribution of PMCA makes its role in the mineralization process unlikely and suggests a role in calcium homeostasis following signaling events [6].

Anatomical context of ATP2B1

• The SERCA is mainly distributed in Purkinje neurons, whereas the PMCA seems to be expressed initially in climbing fibers, shifting to soma and spiny branchlets of Purkinje cells at late embryonic stages [4].
• These findings describe a previously unrecognized location for PMCA in the membranes of cholinergic synaptic vesicles [2].
• In contrast, PMCA expression peaks at 8 days of culture, early in osteoblast differentiation, but declines thereafter [6].
• Moreover, PMCA immunoreactivity co-localized with immunoreactivity for enkephalin and substance P, two neuropeptides known to be expressed in Edinger-Westphal synaptic terminals [2].
• Immunoblot analysis confirmed that 5F10 recognizes a protein with the correct molecular mass for PMCA in tissue homogenates of chick cerebellum, chick ciliary ganglia, and Torpedo synaptic vesicles [2].

Associations of ATP2B1 with chemical compounds

• In immunodot assays, synaptic vesicles purified from Torpedo electric organ are also immunoreactive for PMCA as well as SV-2 [2].

Analytical, diagnostic and therapeutic context of ATP2B1

• Northern blots of intestinal poly(A)+ RNA with 32P-labeled DNA showed the presence of three major species of chicken PMCA mRNAs at about 6.6, 5.4, and 4.5 kb [1].

References