Disease relevance of ARL4D

• These results indicate that these two ARF4L peptides could be targets for immunotherapy of HLA-A2+ patients with brain tumors [1].
• To elucidate the molecular mechanisms underlying post-ischemic phenomena including delayed neuronal death, we screened for genes which were induced in the hippocampus after transient global ischemia in the Mongolian gerbil by a differential display method, and cloned a gerbil homologue of human ADP-ribosylation factor 4L (ARF4L) [2].
• The expression of ARF4L mRNA was elevated at 12 h after hypoxia exposure, similarly to HSP70 [2].

High impact information on ARL4D

• Role of ARF4L in recycling between endosomes and the plasma membrane [3].
• The human ADP-ribosylation factor-like protein, ARF4L is a member of the ARF family, which are small GTP-binding proteins that play significant roles in vesicle transport and protein secretion [3].
• Moreover, the inactive-form of ARF4L (T35N) causes localization of transferrin receptors to the endosomal compartment, while the active form (Q80L) causes transport to the plasma membrane [3].
• Expression of an ADP-ribosylation factor like gene, ARF4L, is induced after transient forebrain ischemia in the gerbil [2].
• To determine the cause of the induction of ARF4L gene expression after transient ischemia, we examined the changes in ARF4L mRNA expression in HEK 293 cells under hypoxic conditions compared with HSP70 [2].

Biological context of ARL4D

• These results will help to elucidate the association of upregulation of vesicle transport systems including ARF4L and stress responses of neurons after transient ischemia [2].
• On the other hand, in the CA1 region where cell death occurs in this model, ARF4L mRNA was slightly detected from 1 to 2 days after ischemia but was absent after 3 days [2].
• Although the physiological roles of ARF4L are unknown, it is likely that ARF4L participates in vesicle transport between the endoplasmic reticulum (ER) and Golgi complex as it contains a GTP binding site, myristoylation site and coatmer binding motif (KKXX) [2].
• Among ARLs, ARL6 which was initially isolated from a J2E erythroleukemic cell line is divergent in its consensus sequences and its expression has been shown to be limited to the brain and kidney in adult mouse (Ingley, 1999) [4].

Anatomical context of ARL4D

• In situ hybridization analysis indicated that the expression of ARF4L mRNA was elevated in neurons of the dentate gyrus (DG) and CA1 regions [2].
• These findings indicate that ARF4L drive the transport of cargo protein and subsequent fusion of recycling vesicles with the plasma membrane for maintenance of the cell surface [3].
• Here, we investigated the expression pattern of ARL6 during early mouse development by whole-mount in situ hybridization and found that interestingly, ARL6 mRNA was localized around the node at 7.0-7.5 days post coitum (dpc) embryos, while weak expression was also found in the ectoderm [4].

References