Escaping the endoplasmic reticulum: why does a molecular chaperone leave home for greener pastures?

Abstract

Molecular chaperones reside in nearly every organelle within a eukaryotic cell, and in each of these compartments, they ensure that protein homeostasis (or proteostasis) is maintained. In this issue, Wiseman and colleagues find that an ER lumenal chaperone escapes this compartment when a specific stress pathway is activated. The chaperone, an Hsp40 homolog known as ERdj3, transits through the secretory pathway to the extracellular space. During this journey, ERdj3 can escort an aggregation‐prone protein or it can identify aggregation‐prone proteins extracellularly, thereby functioning outside of its normal environment.

Human mitochondrial pyruvate carrier 2 as an autonomous membrane transporter

“…The choice for asolectin was based on previous literature 23 . Two independent approaches were adopted to demonstrate the protein-mediated substrate transport: (i) the canonical quantification of the increase in intravesicular 14 C-labelled pyruvate 2 , 3 , 6 , 15 and (ii) the quantification of the decrease in extravesicular pyruvate, as indicated by the enzymatic activity of lactate dehydrogenase A (LDHA) (Supp. Figure 3C ).…”

“…Nearly four decades after the demonstration of the protein-mediated transport of pyruvate across the inner mitochondrial membrane (IMM) 1 , two concurrent studies identified the oligomeric complex formed by MPC1 and MPC2 as necessary and sufficient for this task 2 , 3 ; MPC1 and MPC2 were proposed to function together via the formation of an oligomeric structure of approximately 150 kDa 2 . These original findings inspired many subsequent investigations that have further characterized MPC-dependent pyruvate transport in the cellular context 4 – 6 , with multiple groups showing that either the loss of MPC1 or MPC2 in mitochondria is sufficient to confer similar loss of function phenotypes 6 – 11 . However, to date, the isolation and reconstitution of MPC1:MPC2 into proteoliposomes is still considered necessary to perform the ultimate proof-of-concept experiment to measure pyruvate transport 9 , 12 , 13 .…”

Glucocorticoid receptor signalling activates YAP in breast cancer

“…The metadaset of breast cancer gene expression profiles has been created starting from a collection of 4,640 samples from 27 major data sets, comprising microarray data of breast cancer samples annotated with histological tumour grade and clinical outcome1767. The collection was normalized and annotated with clinical information as described in ref.…”

“…The collection was normalized and annotated with clinical information as described in ref. 67. This resulted in a compendium comprising 3,661 unique samples from 25 independent cohorts.…”

In Silico Screening of the Human Gut Metaproteome Identifies Th17-Promoting Peptides Encrypted in Proteins of Commensal Bacteria

“…On the other hand, surface proteins like the sortase-dependent pili from B. bifidum PRL2010 induced a Th1 response ( Turroni et al, 2013 ). Other surface-associated protein are more related in regulating inflammatory responses such as Lactobacillus acidophilus S-layer A, which has been shown to protect mouse against experimentally induced colitis through a specific interaction with SIGNR3 ( Lightfoot et al, 2015 ). Treg cells have become one of the main focuses of study in immune modulation properties of probiotics, and the balance between Treg/Th responses plays a key role in the maintenance of gut homeostasis ( Maloy and Powrie, 2011 ).…”