Issues

Summary: We discuss how the co-chaperone BAG3 maintains the proteome by balancing transcription, translation and autophagy, and how impairment or deregulation of BAG3 can cause muscle weakness, neurodegeneration and cancer.

Summary: This Review discusses emerging evidence suggesting that condensed states of living matter regulate intracellular organization, metabolism, signaling and stress adaptation.

Highlighted Article: Trim33, a transcriptional regulator known to modulate TGF-β signalling and hematopoiesis, is essential for the mobilization of macrophages and neutrophils towards developmental or inflammatory cues.

Summary: In contrast to canonical Shc-mediated signalling, ShcD promotes stimulus-independent phosphorylation, ubiquitylation, and internalisation of the EGFR, thereby altering cellular sensitivity to ligand.

Highlighted Article: The mechanism by which STIM1 molecules transmit information on changes in ER Ca²⁺ concentration involves a conformational change in the CC1 domain of the cytoplasmic segment of dimeric STIM1 molecules rather than oligomerization.

Summary: Muscles from nestin-knockout mice have decreased mass, are prone to spontaneous degeneration/regeneration and have longer recovery time after injury. This phenotype is linked to disturbed proliferation of satellite cells.

Highlighted Article: SIDT2 localization to the lysosomal membrane is mediated by three YxxΦ motifs. SIDT2 targeting to lysosomes via these motifs is necessary for SIDT2 function in RNautophagy, a novel RNA degradation system.

Summary: Deletion of inositol hexakisphosphate kinase 1 (IP6K1) results in the absence of chromatoid bodies and premature translation of Tnp2 and Prm2, leading to arrested differentiation in mouse spermatids.

Highlighted Article: The proto-oncogenic E3 ubiquitin ligase NEDD4 induces ubiquitylation and lysosomal degradation of connexin 43, a protein that is often dysregulated during cancer development, resulting in loss of gap junctions in human carcinoma cells.

Summary: Multiple ubiquitin E2 enzymes involved in cytomegalovirus US2-mediated ERAD of immunoreceptors are identified. UBE2G2 is required for ERAD, whereas UBE2J2 counteracts it by downregulating the crucial TRC8 ubiquitin ligase.

Highlighted Article: COPII components mediate the formation of transport carriers from the ER. Fluorescence microscopy analysis of artificial planar membrane is used to define the dynamics of COPII coat polymerization.

Summary: The pro-apoptotic BCL-2 protein BAX is inhibited by retrotranslocation into the cytosol. The E3 ligase parkin targets misregulated BAX on the mitochondria for proteasomal degradation.

Summary: The ERM protein ezrin directly interacts with AQP2 facilitating AQP2 endocytosis, thus linking the dynamic regulation of actin cytoskeleton network with AQP2 trafficking.

Summary: ChIP is the standard technique to study chromatin. We propose a high-resolution microscopy tool to visualize changes in histone modifications, RNA transcription and nuclear architecture at single-nucleus level in real time.