Procollagen export from the endoplasmic reticulum

Malhotra, Vivek; Erlmann, Patrik; Nogueira, Cristina

doi:10.1042/bst20140286

Cited by 35 publications

(33 citation statements)

References 27 publications

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“…For large cargo such as procollagens and prechylomicrons, systems that recognize the cargo and promote the formation of larger vesicles are needed (Malhotra et al 2015). The inclusion of large membrane protein clusters or membrane proteins with awkward geometries may also require special arrangements.…”

Section: Bulky Cargomentioning

confidence: 99%

Cargo Capture and Bulk Flow in the Early Secretory Pathway

Barlowe

Helenius

2016

Annu. Rev. Cell Dev. Biol.

175

191

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Transport of newly synthesized proteins from the endoplasmic reticulum (ER) to the Golgi complex is highly selective. As a general rule, such transport is limited to soluble and membrane-associated secretory proteins that have reached properly folded and assembled conformations. To secure the efficiency, fidelity, and control of this crucial transport step, cells use a combination of mechanisms. The mechanisms are based on selective retention of proteins in the ER to prevent uptake into transport vesicles, on selective capture of proteins in COPII carrier vesicles, on inclusion of proteins in these vesicles by default as part of fluid and membrane bulk flow, and on selective retrieval of proteins from post-ER compartments by retrograde vesicle transport.

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Section: Bulky Cargomentioning

confidence: 99%

Cargo Capture and Bulk Flow in the Early Secretory Pathway

Barlowe

Helenius

2016

Annu. Rev. Cell Dev. Biol.

175

191

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“…The expression plasmids for MIA3/TANGO1 , pcDNA3.1(+)-TANGO1-HA, were as described previously [12, 14, 17–20] and kindly provided by Dr. Vivaek Malhotra and colleagues.…”

Section: Methodsmentioning

confidence: 99%

Identification of a molecular signaling gene-gene regulatory network between GWAS susceptibility genes ADTRP and MIA3/TANGO1 for coronary artery disease

Luo

Wang

Ren

et al. 2017

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Coronary artery disease (CAD) is the leading cause of death worldwide. GWAS have identified >50 genomic loci for CAD, including ADTRP and MIA3/TANGO1. However, it is important to determine whether the GWAS genes form a molecular network. In this study, we have uncovered a novel molecular network between ADTRP and MIA3/TANGO1 for the pathogenesis of CAD. We showed that knockdown of ADTRP expression markedly down-regulated expression of MIA3/TANGO1. Mechanistically, ADTRP positively regulates expression of PIK3R3 encoding the regulatory subunit 3 of PI3K, which leads to activation of AKT, resulting in up-regulation of MIA3/TANGO1. Both ADTRP and MIA3/TANGO1 are involved in endothelial cell (EC) functions relevant to atherosclerosis. Knockdown of ADTRP expression by siRNA promoted oxidized-LDL-mediated monocyte adhesion to ECs and transendothelial migration of monocytes, inhibited EC proliferation and migration, and increased apoptosis, which was reversed by expression of constitutively active AKT1 and MIA3/TANGO1 overexpression, while the over-expression of ADTRP in ECs blunted these processes. Knockdown of MIA3/TANGO1 expression also promoted monocyte adhesion to ECs and transendothelial migration of monocytes, and vice versa for overexpression of MIA3/TANGO1. We found that ADTRP negatively regulates the levels of collagen VII and ApoB in HepG2 and endothelial cells, which are downstream regulatory targets of MIA3/TANGOI. In conclusion, we have uncovered a novel molecular signaling pathway for the pathogenesis of CAD, which involves a novel gene-gene regulatory network. We show that ADTRP positively regulates PIK3R3 expression, which leads to activation of AKT and up-regulation of MIA3/TANGO1, thereby regulating endothelial cell functions directly relevant to atherosclerosis.

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“…The secretory pathway has also adapted itself to the transport of specialized cargoes and the needs of specialized organelles. Recent research, for example, reveals fascinating mechanisms that are deployed to transport very large cargoes, such as polymers of newly synthesized collagen, which could not be physically accommodated within the confines of the carrier vesicles that transport standard cargoes between the secretory pathway’s stations (Venditti et al , 2012; Lavieu et al , 2014; Malhotra et al , 2015). Furthermore, at least some proteins, including a subset of those that populate the membrane of the primary cilium, appear to pursue a variant version of the secretory pathway via which they bypass some or all of the structures of the Golgi complex (Hoffmeister et al , 2011; Prydz et al , 2013; Tian et al , 2014).…”

Section: The Next 50 Years: How Does the Secretory Pathway Work And Wmentioning

confidence: 99%

The secretory pathway at 50: a golden anniversary for some momentous grains of silver

Matlin

Caplan

2017

MBoC

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The secretory pathway along which newly synthesized secretory and membrane proteins traffic through the cell was revealed in two articles published 50 years ago. This discovery was the culmination of decades of effort to unite the power of biochemical and morphological methodologies in order to elucidate the dynamic nature of the cell’s biosynthetic machinery. The secretory pathway remains a central paradigm of modern cell biology. Its elucidation 50 years ago inspired tremendous multidisciplinary and on-going efforts to understand the machinery that makes it run, the adaptations that permit it to serve the needs of specialized cell types, and the pathological consequences that arise when it is perturbed.

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Procollagen export from the endoplasmic reticulum

Cited by 35 publications

References 27 publications

Cargo Capture and Bulk Flow in the Early Secretory Pathway

Cargo Capture and Bulk Flow in the Early Secretory Pathway

Identification of a molecular signaling gene-gene regulatory network between GWAS susceptibility genes ADTRP and MIA3/TANGO1 for coronary artery disease

The secretory pathway at 50: a golden anniversary for some momentous grains of silver

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