Disease relevance of Gm2a

• It is well established, however, that the lysosomes of I-cell disease (ICD) patients have near normal levels of several lysosomal proteins, including prosaposin and GM2AP [1].

High impact information on Gm2a

• The Gm2a -/- mice demonstrated neuronal storage but only in restricted regions of the brain (piriform, entorhinal cortex, amygdala, and hypothalamic nuclei) reminiscent of the asymptomatic Tay-Sachs model mice [2].
• These genes include prepro-enkephalin, GM2 ganglioside activator protein, glucocorticoid-induced TNFR superfamily member 18, and integrin alpha(E)beta(7) [3].
• The mouse gene encoding the GM2 activator protein (Gm2a): cDNA sequence, expression, and chromosome mapping [4].
• In addition, a Gm2a-related sequence (Gm2a-rs1) was mapped to mouse Chr 5 [4].
• Expression of the Gm2a transcript (approximately 2.3 kb) was apparent in all tissues examined and was most abundant in kidney and testis [4].

Biological context of Gm2a

• Gm2a was mapped to Chromosome (Chr) 11, where it co-segregated with Csfgm [5].
• To understand better factors affecting the expression of the GM2 activator protein gene (Gm2a) in mouse tissues, we have determined its exon-intron organization and analyzed its promoter region [5].
• Gm2a is about 14 kb, has four exons, and the 5' flanking region contains a CAAT box, Sp1 binding sites, AP-1, AP-2 sites, and a pair of IRE sites [5].

Anatomical context of Gm2a

• Interestingly, dominant-negative GGAs, unable to bind clathrin to shuttle from the Golgi, prevented the trafficking of prosaposin and GM2AP to lysosomes [1].
• Prosaposin (SGP-1) and GM2 activator protein (GM2AP) are soluble sphingolipid activator proteins (SAPs) that are targeted to the lysosomal compartment of Sertoli cells to aid hydrolases in the breakdown of glycosphingolipids [1].

Other interactions of Gm2a

• Similarities between the elements present in Gm2a and Hexa promoters might in part explain their similar expression patterns in mouse tissues [5].
• Thus, prosaposin and GM2AP can traffic to lysosomes in a MPR independent manner [1].
• In conclusion, our results showed that the trafficking of prosaposin and GM2AP to the lysosome is dependent on sortilin [1].

Analytical, diagnostic and therapeutic context of Gm2a

• With reverse transcriptase-polymerase chain reaction (RT-PCR), mRNA for SAP 4 and SAP6 were detected in the stomach of all mice, whereas SAP2, SAP3 and SAP5 mRNA were detected not in all animals and SAP1 mRNA was not detectable [6].

References