Table 1.
Different functions of IRE1α in cellular physiology.
| Physiological Role | Mechanism | Model/Tissue Region | References |
|---|---|---|---|
| Tissue growth | Inducing XBP1s dependent function. | Liver | [91] |
| Lipogenesis | Regulates lipogenic gene expression involved in serum cholesterol triglyceride and free fatty acid synthesis. | Liver | [92] |
| Secretory function | IRE1 deletion impaired the insulin, saliva, and antibody secretion. | Exocrine glands, plasma cell, pancreatic acinar and β cells, salivary serous tissues |
[93,94,95] |
| Lipid metabolism | IRE1β-mediated RIDD activity on MTP and reduce dyslipidemia. | Mice/Liver | [96,97] |
| Lipid, glucose, and bile acid metabolism | Deletion of hepatic XBP1 disables the bile acid metabolism in mice. | Liver | [94,98] |
| Organelle biogenesis and homeostasis | IRE1/XBP1 increases the synthesis of membrane phospholipids, especially in secretory cells and fibroblasts to carry out their huge task to meet the physiological demand. |
Endoplasmic reticulum | [99,100,101] |
| B cell differentiation | XBP1s dependent function, deletion impaired differentiation. | Lymphoid tissue | [102] |
| Eosinophil differentiation | XBP1s dependent function, deletion impaired differentiation. | myeloid tissue granulocyte | [103] |
| Embryogenesis | IRE1α, IRE1β function in mesoderm development, XBP1 dependent pathway. | Human/Xenopus laevis. Mesoderm, gut |
[104,105,106] |
| Osteoclastogenesis | IRE1α/XBP1-mediated osteoblast and osteoclast differentiation, induction of bone morphogenetic protein-2 and PTHR. | Osteoblast, Osteoclast | [107,108,109] |
| Immune cell development | IRE1α/XBP1 functions, deletion impaired antigen presentation to T cells, proliferation, and differentiation. Loss of RIDD and XBP1 causes the cDC1 cell death. | Dendritic cells, Lung and small intestine |
[110] |
| Cell cycle regulation | IRE1α /XBP1 drives cells from G1 to S-phase through regulation of cyclin A1 and D1, promote compensatory proliferation of β-cells. | Pancreatic β cells | [111,112] |
| Photoreceptor differentiation | IRE1α /RIDD level and increased the delivery of rhodopsin-1 to the rhabdomere. Loss of IRE1α disrupted the rhabdomere morphogenesis and the ER anatomy. |
Drosophila compound eye R cells | [113,114] |
| Chondrocyte differentiation | IRE1α negatively regulates chondrocyte differentiation through inhibition of granulin-epithelin precursor (GEP) and by upregulating parathyroid hormone-related peptide (PTHrP). | Chondrocyte | [109,115] |
| Dendrite morphogenesis | Perturbation of the IRE1 pathway causes loss of dendritic branches. | Caenorhabditis elegans/neurons | [116,117] |
| Enterocytes | IRE1β inhibited the differentiation of Caco-2 cells into enterocyte-like cells by suppressing microsomal triglyceride transfer protein (MTP). | Intestine | [43] |
| Mucous secretion | IRE1β knockout mice are viable, but are more susceptible to colitis. IRE1β is needed to maintain normal transcription rates of mucin genes and genes associated with the development of mucins. |
Intestine goblet cells, gut epithelium, airway epithelium |
[5,6,118] |
| Metabolic transformation of cells | IRE1/XBP1 pathway contributes to lipogenic gene expression during locational metabolism and lipid metabolism by controlling liver hormone; fibroblast growth factor 21(FGF21). | Mammary gland, Liver, adipocytes | [119,120,121] |
| Tissue regeneration | IRE1/XBP1 through direct regulation of transcription factor STAT3. | Mice/hepatocyte | [122] |
| Hematopoietic cells | IRE1/XBP1 pathway plays a role in cell cycle, differentiation of hematopoietic cell. | Hematopoietic tissue | [123] |