Ubiquitin-dependent regulation of COPII coat size and function

Department of Molecular and Cell Biology, University of California at Berkeley, California 94720, USA.
Nature (Impact Factor: 42.35). 02/2012; 482(7386):495-500. DOI: 10.1038/nature10822
Source: PubMed

ABSTRACT Packaging of proteins from the endoplasmic reticulum into COPII vesicles is essential for secretion. In cells, most COPII vesicles are approximately 60-80 nm in diameter, yet some must increase their size to accommodate 300-400 nm procollagen fibres or chylomicrons. Impaired COPII function results in collagen deposition defects, cranio-lenticulo-sutural dysplasia, or chylomicron retention disease, but mechanisms to enlarge COPII coats have remained elusive. Here, we identified the ubiquitin ligase CUL3-KLHL12 as a regulator of COPII coat formation. CUL3-KLHL12 catalyses the monoubiquitylation of the COPII-component SEC31 and drives the assembly of large COPII coats. As a result, ubiquitylation by CUL3-KLHL12 is essential for collagen export, yet less important for the transport of small cargo. We conclude that monoubiquitylation controls the size and function of a vesicle coat.

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Available from: Kanika Bajaj Pahuja, Aug 24, 2015
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    • "However, as described above, the same E3 complex is also involved in ubiquitin-dependent proteolysis of other substrates like Gli2/3 (Chen et al, 2009a) or SRC-3 (Li et al, 2011), most likely via K48-linked polyubiquitin chains. Similarly, Aurora B and caspase-8 are regulated by nonproteolytic ubiquitylation and Sec31A and PLK1 are monoubiquitylated by CRL3s in human cells (Jin et al, 2009, 2012; Maerki et al, 2009; Beck et al, 2013). Another interesting example is the light intensity-dependent differential regulation of poly-versus mono-/multi-mono-ubiquitylation of PHOT1 by CRL3-NPH3 in plants (Roberts et al, 2011). "
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    ABSTRACT: Protein ubiquitylation is a post-translational modification that controls all aspects of eukaryotic cell functionality, and its defective regulation is manifested in various human diseases. The ubiquitylation process requires a set of enzymes, of which the ubiquitin ligases (E3s) are the substrate recognition components. Modular CULLIN-RING ubiquitin ligases (CRLs) are the most prevalent class of E3s, comprising hundreds of distinct CRL complexes with the potential to recruit as many and even more protein substrates. Best understood at both structural and functional levels are CRL1 or SCF (SKP1/CUL1/F-box protein) complexes, representing the founding member of this class of multimeric E3s. Another CRL subfamily, called CRL3, is composed of the molecular scaffold CULLIN3 and the RING protein RBX1, in combination with one of numerous BTB domain proteins acting as substrate adaptors. Recent work has firmly established CRL3s as major regulators of different cellular and developmental processes as well as stress responses in both metazoans and higher plants. In humans, functional alterations of CRL3s have been associated with various pathologies, including metabolic disorders, muscle, and nerve degeneration, as well as cancer. In this review, we summarize recent discoveries on the function of CRL3s in both metazoans and plants, and discuss their mode of regulation and specificities.
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    • "Under these conditions, cryoelectron microscopy has documented the oligomerization of viral glycoproteins. Large protein assemblies like these and like collagen may require modification of the vesicle formation process to accommodate the larger proteins (Malhotra and Erlmann, 2011; Jin et al, 2012). Thus, it was especially interesting that collagen and VSV-G protein are not detected in PAUFcontaining vesicles en route to the cell surface. "
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