9.B.113 The Collagen Secretory Protein, Mia3 (Mia3) Family
Melanoma inhibitory activity member 3 (MIA3/TANGO1) is an evolutionarily conserved endoplasmic reticulum resident transmembrane protein. Recent in vitro studies have shown that it is required for the loading of collagen VII into COPII-coated transport vesicles. Wilson et al. (2011) showed that mice lacking Mia3 are defective for the secretion of numerous collagens, including collagens I, II, III, IV, VII, and IX. Collagen deposition by these cell types is abnormal, and the extracellular matrix composition is compromised. These changes are associated with intracellular accumulation of collagen and the induction of a strong unfolded protein response, primarily within the developing skeleton. Chondrocyte maturation and bone mineralization are severely compromised in Mia3-null embryos, leading to dwarfism and neonatal lethality. Thus, Mia3 may be required for the efficient secretion of all collagens in higher organisms (Wilson et al., 2011).