Axonal endoplasmic reticulum tubules control local translation via P180/RRBP1-mediated ribosome interactions.

Local mRNA translation in axons is critical for the spatiotemporal regulation of the axonal proteome. A wide variety of mRNAs are localized and translated in axons; however, how protein synthesis is regulated at specific subcellular sites in axons remains unclear. Here, we establish that the axonal endoplasmic reticulum (ER) supports axonal translation in developing rat hippocampal cultured neurons.

A general role for TANGO1, encoded by MIA3, in secretory pathway organization and function.

Complex machinery is required to drive secretory cargo export from the endoplasmic reticulum (ER), which is an essential process in eukaryotic cells. In vertebrates, the MIA3 gene encodes two major forms of transport and Golgi organization protein 1 (TANGO1S and TANGO1L), which have previously been implicated in selective trafficking of procollagen. Using genome engineering of human cells, light microscopy, secretion assays, genomics and proteomics, we show that disruption of the longer form, TANGO1L, results in relatively minor defects in secretory pathway organization and function, including having limited impacts on procollagen secretion.

ER-to-Golgi Transport: A Sizeable Problem.

Metazoans require efficient and ordered secretion of extracellular matrix (ECM) to coordinate cell and tissue function. Many ECM proteins are atypically large and their demand during key stages of development presents a major challenge to the canonical secretion machinery. While many of the molecular players in this pathway are known, little is understood about how they are integrated in time and space.

Developing pathways to clarify pathogenicity of unclassified variants in Osteogenesis Imperfecta genetic analysis.

Background: With increased access to genetic testing, variants of uncertain significance (VUS) where pathogenicity is uncertain are being increasingly identified. More than 85% Osteogenesis Imperfecta (OI) patients have pathogenic variants in COL1A1/A2. However, when a VUS is identified, there are no pathways in place for determining significance.

ER-to-Golgi trafficking of procollagen in the absence of large carriers.

Secretion and assembly of collagen are fundamental to the function of the extracellular matrix. Defects in the assembly of a collagen matrix lead to pathologies including fibrosis and osteogenesis imperfecta. Owing to the size of fibril-forming procollagen molecules it is assumed that they are transported from the endoplasmic reticulum to the Golgi in specialized large COPII-dependent carriers.

COPII-dependent ER export in animal cells: adaptation and control for diverse cargo.

The export of newly synthesized proteins from the endoplasmic reticulum is fundamental to the ongoing maintenance of cell and tissue structure and function. After co-translational translocation into the ER, proteins destined for downstream intracellular compartments or secretion from the cell are sorted and packaged into transport vesicles by the COPII coat protein complex. The fundamental discovery and characterization of the pathway has now been augmented by a greater understanding of the role of COPII in diverse aspects of cell function.

Regulator of calcineurin-2 is a centriolar protein with a role in cilia length control.

Almost every cell in the human body extends a primary cilium. Defective cilia function leads to a set of disorders known as ciliopathies, which are characterised by debilitating developmental defects that affect many tissues. Here, we report a new role for regulator of calcineurin 2 (RCAN2) in primary cilia function.

recurrent missense mutation causing Cole-Carpenter syndrome.

Background: Cole-Carpenter syndrome (CCS) is commonly classified as a rare Osteogenesis Imperfecta (OI) disorder. This was following the description of two unrelated patients with very similar phenotypes who were subsequently shown to have a heterozygous missense mutation in .

Objectives: Here, we report a 3-year old female patient with severe OI who on exome sequencing was found to carry the same missense mutation in as reported in the original cohort.

TFG Promotes Organization of Transitional ER and Efficient Collagen Secretion.

Collagen is the most abundant protein in the animal kingdom. It is of fundamental importance during development for cell differentiation and tissue morphogenesis as well as in pathological processes such as fibrosis and cancer cell migration. However, our understanding of the mechanisms of procollagen secretion remains limited.