Identification of an S-adenosylhomocysteine hydrolase-like transcript induced during dendritic cell differentiation

Abstract

Dendritic cells (DC) are the professional antigen-presenting cells that initiate immune responses. While DC take up antigen, migrate to lymph nodes and present processed antigen to T lymphocytes, little is known of the intracellular biochemical pathways controlling these events. Using the differential display technique, employing the activated blood DC-like cell line L428, we isolated a cDNA induced during DC differentiation likely to have a regulatory function. This cDNA encoded a putative 530-amino-acid (aa) protein consisting of a unique hydrophilic domain (106 aa) and a domain (424 aa) similar to the methylation pathway enzyme S-adenosylhomocysteine hydrolase (AHCY). Therefore, this molecule was termed DC-expressed AHCY-like molecule (DCAL). DCAL mRNA was expressed moderately in fresh blood DC, but was not detectable in other peripheral blood mononuclear cells. DCAL mRNA increased markedly during activation of blood and skin DC (Langerhans cells), but was diminished in terminally differentiated tonsil DC. Cultured monocytes expressed little DCAL mRNA, but levels increased markedly when differentiated into DC by cytokines GM-CSF and IL-4. The DCAL gene [Chromosome (Chr) 1] and another previously identified DCAL-like molecule KIAA0828 (Chr 7) differed from the AHCY gene (Chr 20) in gene organization. Thus, DCAL may have a role in controlling critical events in DC differentiation and belong to a novel family of AHCY-like molecules.

Homocysteine enhances cardiac neural crest cell attachment in vitro by increasing intracellular calcium levels

“…IP 3 receptor binding protein released with inositol 1,4,5-trisphosphate (IRBIT; Ando et al, 2003Ando et al, , 2006, also called adenosyl homocysteine hydrolase-like protein 1 (AHCYL1; Dekker et al, 2002), suppresses Ca 2ϩ release from IP 3 receptor channels by directly competing with IP 3 for binding. IRBIT/AHCYL1 has two domains, an N-terminal domain that binds to the IP 3 receptor channel, and a C-terminal domain with 51% identity and 74% similarity to the enzyme adenosyl-homocysteine hydrolase (also called S-adenosylhomocysteine hydrolase).…”

IRBIT, Inositol 1,4,5-Triphosphate (IP3) Receptor-binding Protein Released with IP3, Binds Na+/H+ Exchanger NHE3 and Activates NHE3 Activity in Response to Calcium

“…IRBIT/AdoHcyL1 shares 51% identity (74% similarity) to AdoHcy and it is ubiquitously expressed (4). The importance of IRBIT/AdoHcyL1 remains incompletely understood, but its expression is elevated during dendritic cell differentiation (32). Ectopic expression of IRBIT/AdoHcyL1 in zebrafish embryos induced dorsalization, whereas gene silencing of IRBIT/ AdoHcyL1 induced ventralized morphologies, none of which could be mimicked by the manipulation of AdoHcy gene expression, suggesting distinct functions by IRBIT from AdoHcy (33).…”

The IRBIT domain adds new functions to the AHCY family

“…Noteworthy, human and mouse AHCY is encoded by only 10 exons and its exon-intron junction organization differs strikingly from the one of the AHCY domain of AHCYL1. (28) The gene structure of AHCYL2 closely resembles the one of AHCYL1, with the exception of the additional P/A domain-encoding exons. This indicates that the AHCY-like proteins are evolutionary distinct from AHCY.…”

“…This indicates that the AHCY-like proteins are evolutionary distinct from AHCY. (28) Alternative splicing of zebrafish AHCYL1 gives rises to two AHCYL1 isoforms: AHCYL1-A and AHCYL1-B.…”

“…AHCYL1 mRNA expression is strongly induced upon dendritic cell (DC) activation, and hence the corresponding protein was also termed DC-expressed AHCY-like molecule (DCAL). (28) Human and mouse AHCYL1…”