Tissue‐Specific Expression of Isoaspartyl Protein Carboxyl Methyltransferase Gene in Rat Brain and Testis

Abstract

lsoaspartyl protein carboxyl methyltransferase (PIMT) is widely distributed in mammalian tissues. Using a polymerase chain reaction-generated 124-bp DNA fragment from brain cDNA as a probe, four different sizes (-4.0, 2.5, 1.7, and 1.1 kb) of transcripts were detected with northern blot analysis. They were expressed predominantly in rat brain and testis. The major transcripts were 2.5 and 1.7 kb in the brain and 2.5 and 1.1 kb in the testis. One of the major transcripts specific to the testis (1.1 kb) was determined to study the structural difference of major transcripts in the two tissues. This testicular cDNA had neither the 5 (94 nucleotides) nor the 3 (594 nucleotides) end of previously reported brain cDNA corresponding to 1.7 kb. The mRNA levels and enzyme activities of different regions and developmental changes were examined in the brain. The mRNA levels and enzyme activities were concomitantly high in cerebral cortex and hippocampus. Although they increased rapidly -30 days after birth in the testis and decreased in aged rats, they increased gradually after birth and remained high during the aging of the brain. Both structural and developmental studies show that the expression of the PIMT gene in brain and testis is regulated in a tissue-specific manner. Key Words: Isoaspartyl protein carboxyl methyltransferase-mRNA-Postnatal development-Rat brain and testis-cDNA sequence-Polymerase chain reaction.

The protein l-isoaspartyl-O-methyltransferase functions in the Caenorhabditis elegans stress response

“…pcm-1 was previously determined to be a member of Mount 6, a group or “mountain” of genes transcribed at high levels in neuronal cells (Kim et al ., 2001). Neural and reproductive tissue pcm-1 expression pattern in worms parallels the pattern found in rat where the homolog is highly expressed in the brain and testes (Mizobuchi et al, 1994). …”

Isoaspartyl Formation in Creatine Kinase B Is Associated with Loss of Enzymatic Activity; Implications for the Linkage of Isoaspartate Accumulation and Neurological Dysfunction in the PIMT Knockout Mouse

“…Continuing cycles of PIMT action efficiently repair L-isoAsp sites in vitro [23]–[25], while reduction of PIMT activity in cultured cells or knockout (KO) mice dramatically increases the level of isoAsp-containing proteins [26]–[29]. PIMT is widely distributed in mammalian tissues, but is particularly rich in the CNS [30]–[33]. The critical need for PIMT in brain is evident from the overt neurological phenotype of PIMT-deficient mice; increased brain size, abnormal neuro-anatomical and electrophysiological properties of hippocampal cells along with reduced cognitive function [34], atypical open-field behavior [35], and fatal epileptic seizures beginning at 4 weeks of age [27], [28].…”

Isoaspartylation appears to trigger small cell lung cancer-associated autoimmunity against neuronal protein ELAVL4

“…While PIMT is present in all mammalian tissues, it is most prominent in the brain, retina, and testis (Diliberto and Axelrod, 1976; Mizobuchi et al, 1994; Qin et al, 2014). PIMT is crucial for normal neuronal activity; mice lacking the enzyme show a dramatic increase in protein isoaspartylation in the brain and die of seizures a few weeks after birth (Kim et al, 1997; Yamamoto et al, 1998; Desrosiers and Fanelus, 2011).…”