Coatomer

COPII is a coatomer that coats the vesicles transporting proteins from the ER to the golgi complex.^[4] This pathway is referred to as anterograde transport.^[4] The first step in the COPII pathway is the recruitment of a small GTPase named Sar1 to the ER membrane.^[9] Once Sar1 interacts with the ER membrane, a membrane protein called Sec12 acts a guanine nucleotide exchange factor and substitutes GDP for GTP on Sar1.^[9] This activates the Sar1 protein, causing its amphipathic alpha helix to bind to the ER membrane.^[9] Membrane bound Sar1 attracts the Sec23-Sec24 protein heterodimer to the ER membrane. Sar1 directly binds to Sec23 while Sec24 directly binds to the cargo receptor located on the ER membrane.^[10]

The Sar1-GTP and Sec23-24 complex recruits another protein complex called Sec13/Sec31. This complex polymerizes to form the outer layer of the coat.^[10] COP II vesicles must shed their coat before they can fuse with the cis-Golgi membrane. This occurs when the GTP on Sar1 is hydrolyzed by the GTPase activating protein.^[10] Activation of the GTPase also reverses the interaction between Sar1 and the Sec23-Sec24 protein dimer.^[10] COPII vesicles select the proper cargo by directly interacting with ER export signals that are present in transmembrane ER proteins.^[7] There are several classes of ER export signals that have been identified in various organisms. The involvement of so many different ER export signals means that there are multiple binding sites for the export signals.^[7]

Newly made secretory proteins must pass through the ER and the golgi complex before they can leave the cell. Problems with COPII early secretory pathways can lead to a disease called Congenital Dyserythropoietic Anemia type II.^[11] This is an autosomal recessive disorder that results from the mutation of a gene called Sec23B.^[11] This gene plays an important role in regulating the transport of proteins within cells.^[11] Symptoms for Congenital Dyserythropoietic Anemia type II include anemia, jaundice, low reticulocyte count, splenomegaly, and hemochromatosis.^[12] Congenital Dyserythropoeitic Anemia Type II is normally diagnosed during adolescence or early adulthood.^[12] Congenital Dyserythropoetic Anemia Type II is a very rare disease with only a few hundred cases worldwide.^[12] Treatment for the disease involves blood transfusions, iron therapy, and the removal of the spleen.^[12]

Another disease associated with deficiencies in the COPII pathway is combined factor V and factor VIII deficiency.^[11] In this disease, the person produces Factor V and VIII but they can not transport factor V or VIII into the bloodstream.^[11] This is an autosomal recessive disorder that leads to bleeding symptoms, epistaxis, menorrhagia, and excessive bleeding after trauma.^[13] The disease can be diagnosed after screening tests are analyzed by a specialized healthcare provider.^[13] The mutation of the MCFD2 gene is what causes combined factor V and VIII deficiency.^[13] Treatment for the disease includes administrating frozen plasma and desmopressin to the patient.^[13]