| First Author | Watanabe K | Year | 2021 |
| Journal | Sci Rep | Volume | 11 |
| Issue | 1 | Pages | 8414 |
| PubMed ID | 33863978 | Mgi Jnum | J:313853 |
| Mgi Id | MGI:6707347 | Doi | 10.1038/s41598-021-87884-7 |
| Citation | Watanabe K, et al. (2021) ILDR2 stabilization is regulated by its interaction with GRP78. Sci Rep 11(1):8414 |
| abstractText | Ildr2 was initially identified as a genetic modifier of diabetes susceptibility in B6.DBA Lep(ob) congenic mice, and was associated with decreased beta-cell replication rates, reduced beta-cell mass, and persistent mild hypoinsulinemic hyperglycemia. However, the molecular mechanisms of how the ILDR2 protein is involved in these effects are largely unknown. We sought to identify ILDR2-interacting proteins to further elucidate the molecular mechanisms underpinning ILDR2 function in pancreatic beta-cells. Using TAP tag technology, we purified proteins interacting with ILDR2 in the pancreatic beta-cell line MIN6, and identified the endoplasmic reticulum resident chaperones, GRP78 and PDIA1, as novel proteins interacting with ILDR2. We demonstrated that GRP78 interacted with ILDR2 and was possibly involved in ILDR2 stabilization by inhibiting ubiquitin-proteasome degradation. Additionally, adenoviral ILDR2 knockdown led to reduced glucose-responsive insulin secretion in MIN6 beta-cells, suggesting ILDR2 may be implicated in a new pathway in hypoinsulinemic hyperglycemia. These data provide evidence for a novel association between GRP78 and ILDR2, and suggest GPR78-ILDR2 may a novel target for diabetic therapeutic modulation in decreased insulin secretion. |
