Reactome | Cargo concentration in the ER

Cargo concentration in the ER

Stable Identifier

R-HSA-5694530

Type

Pathway

Species

Homo sapiens

ReviewStatus

5/5

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Computational analysis suggests that ~25% of the proteome may be exported from the ER in human cells (Kanapin et al, 2003). These cargo need to be recognized and concentrated into COPII vesicles, which range in size from 60-90 nm, and which move cargo from the ER to the ERGIC in mammalian cells (reviewed in Lord et al, 2013; Szul and Sztul, 2011). Recognition of transmembrane cargo is mediated by interaction with one of the 4 isoforms of SEC24, a component of the inner COPII coat (Miller et al, 2002; Miller et al, 2003; Mossessova et al, 2003; Mancias and Goldberg, 2008). Soluble cargo in the ER lumen is concentrated into COPII vesicles through interaction with a receptor of the ERGIC-53 family, the p24 family or the ERV family. Each of these families of transmembrane receptors interact with cargo through their lumenal domains and with components of the COPII coat with their cytoplasmic domains and are packaged into the COPII vesicle along with the cargo. The receptors are subsequently recycled to the ER in COPI vesicles through retrograde traffic (reviewed in Dancourt and Barlowe, 2010). Packaging of large cargo such as fibrillar collagen depends on the transmembrane accessory factors MIA3 (also known as TANGO1) and CTAGE5. Like the ERGIC, p24 and ERV cargo receptors, MIA3 and MIA2 (also known as CTAGE5) interact both with the collagen cargo and with components of the COPII coat. Unlike the other cargo receptors, however, MIA3 and MIA2 are not loaded into the vesicle but remain in the ER membrane (reviewed in Malhotra and Erlmann, 2011; Malhotra et al, 2015).

Literature References

PubMed ID	Title	Journal	Year
12941277	Multiple cargo binding sites on the COPII subunit Sec24p ensure capture of diverse membrane proteins into transport vesicles Miller, EA, Beilharz, TH, Malkus, PN, Lee, MC, Hamamoto, S, Orci, L, Schekman, R	Cell	2003
22013193	COPII and COPI traffic at the ER-Golgi interface Szul, T, Sztul, E	Physiology (Bethesda)	2011
21878990	Protein export at the ER: loading big collagens into COPII carriers Malhotra, V, Erlmann, P	EMBO J	2011
25619253	Procollagen export from the endoplasmic reticulum Malhotra, V, Erlmann, P, Nogueira, C	Biochem. Soc. Trans.	2015
20533886	Protein sorting receptors in the early secretory pathway Dancourt, J, Barlowe, C	Annu. Rev. Biochem.	2010
23378591	The highly conserved COPII coat complex sorts cargo from the endoplasmic reticulum and targets it to the golgi Lord, C, Ferro-Novick, S, Miller, EA	Cold Spring Harb Perspect Biol	2013
12819131	Mouse proteome analysis Kanapin, A, Batalov, S, Davis, MJ, Gough, J, Grimmond, S, Kawaji, H, Magrane, M, Matsuda, H, Schönbach, C, Teasdale, RD, Yuan, Z	Genome Res.	2003
12941276	SNARE selectivity of the COPII coat Mossessova, E, Bickford, LC, Goldberg, J	Cell	2003
12426382	Cargo selection into COPII vesicles is driven by the Sec24p subunit Miller, E, Antonny, B, Hamamoto, S, Schekman, R	EMBO J.	2002
18843296	Structural basis of cargo membrane protein discrimination by the human COPII coat machinery Mancias, JD, Goldberg, J	EMBO J.	2008