A balancing act: PHLPP2 fine tunes AKT activity and MYC stability in prostate cancer
PTEN loss stimulates prostate tumor progression by sustaining AKT activation. Nowak et al. (2019. J. Cell Biol. https://doi.org/10.1083/jcb.201902048) surprisingly show that the AKT-suppressing phosphatase PHLPP2 promotes disease progression in the context of dual PTEN and p53 loss by increasing MYC stability. (Source: Journal of Cell Biology)
Source: Journal of Cell Biology - June 2, 2019 Category: Cytology Authors: Toivanen, R., Furic, L. Tags: Spotlight Source Type: research
HDAC6 and Miro1: Another interaction causing trouble in neurons
Myelin-associated glycoprotein and chondroitin sulfate proteoglycans in the extracellular matrix can prevent regeneration of injured axons. In this issue, Kalinski et al. (2019. J. Cell Biol. https://doi.org/10.1083/jcb.201702187) report that inhibition of HDAC6 prevents the deacetylation of Miro1, increases mitochondrial axonal transport, and restores the size of axonal growth cones. (Source: Journal of Cell Biology)
Source: Journal of Cell Biology - June 2, 2019 Category: Cytology Authors: Van Den Bosch, L. Tags: Trafficking Spotlight Source Type: research
Who plays the ferryman: ATG2 channels lipids into the forming autophagosome
Expansion of the autophagosomal membrane requires a mechanism to supply lipids while excluding most membrane proteins. In this issue, Valverde et al. (2019. J. Cell Biol. https://doi.org/10.1083/jcb.201811139) identify ATG2, a member of the autophagy-related protein family, as a lipid transfer protein and provide important novel insights on how autophagosomes grow. (Source: Journal of Cell Biology)
Source: Journal of Cell Biology - June 2, 2019 Category: Cytology Authors: Ktistakis, N. T. Tags: Spotlight Source Type: research
Kota Saito: Getting out and about
Saito studies the mechanisms that control secretion of collagen from the ER. (Source: Journal of Cell Biology)
Source: Journal of Cell Biology - June 2, 2019 Category: Cytology Authors: ODonnell, M. A. Tags: People & amp;amp; Ideas Source Type: research
Correction: IRE1-XBP1 pathway regulates oxidative proinsulin folding in pancreatic {beta} cells
Vol. 217, No. 4, April 2, 2018. 10.1083/jcb.201707143. In the third (HSP90(Cyt)) and fourth (HSP60(Mit)) panels of Fig. 1 B, the rightmost lane (pancreas tissue) was inadvertently trimmed during final preparation of the paper. The... (Source: Journal of Cell Biology)
Source: Journal of Cell Biology - May 5, 2019 Category: Cytology Authors: Tsuchiya, Y., Saito, M., Kadokura, H., Miyazaki, J.-i., Tashiro, F., Imagawa, Y., Iwawaki, T., Kohno, K. Tags: Corrections Source Type: research
GPCR-independent activation of G proteins promotes apical cell constriction in vivo
Heterotrimeric G proteins are signaling switches that control organismal morphogenesis across metazoans. In invertebrates, specific GPCRs instruct G proteins to promote collective apical cell constriction in the context of epithelial tissue morphogenesis. In contrast, tissue-specific factors that instruct G proteins during analogous processes in vertebrates are largely unknown. Here, we show that DAPLE, a non-GPCR protein linked to human neurodevelopmental disorders, is expressed specifically in the neural plate of Xenopus laevis embryos to trigger a G protein signaling pathway that promotes apical cell constriction during...
Source: Journal of Cell Biology - May 5, 2019 Category: Cytology Authors: Marivin, A., Morozova, V., Walawalkar, I., Leyme, A., Kretov, D. A., Cifuentes, D., Dominguez, I., Garcia-Marcos, M. Tags: Cytoskeleton, Cell Signaling, Biochemistry, Development Articles Source Type: research
VE-PTP stabilizes VE-cadherin junctions and the endothelial barrier via a phosphatase-independent mechanism
Vascular endothelial (VE) protein tyrosine phosphatase (PTP) is an endothelial-specific phosphatase that stabilizes VE-cadherin junctions. Although studies have focused on the role of VE-PTP in dephosphorylating VE-cadherin in the activated endothelium, little is known of VE-PTP’s role in the quiescent endothelial monolayer. Here, we used the photoconvertible fluorescent protein VE-cadherin-Dendra2 to monitor VE-cadherin dynamics at adherens junctions (AJs) in confluent endothelial monolayers. We discovered that VE-PTP stabilizes VE-cadherin junctions by reducing the rate of VE-cadherin internalization independently ...
Source: Journal of Cell Biology - May 5, 2019 Category: Cytology Authors: Juettner, V. V., Kruse, K., Dan, A., Vu, V. H., Khan, Y., Le, J., Leckband, D., Komarova, Y., Malik, A. B. Tags: Adhesion, Cell Signaling Articles Source Type: research
Homeostatic scaling of active zone scaffolds maintains global synaptic strength
Synaptic terminals grow and retract throughout life, yet synaptic strength is maintained within stable physiological ranges. To study this process, we investigated Drosophila endophilin (endo) mutants. Although active zone (AZ) number is doubled in endo mutants, a compensatory reduction in their size homeostatically adjusts global neurotransmitter output to maintain synaptic strength. We find an inverse adaptation in rab3 mutants. Additional analyses using confocal, STED, and electron microscopy reveal a stoichiometric tuning of AZ scaffolds and nanoarchitecture. Axonal transport of synaptic cargo via the lysosomal kinesin...
Source: Journal of Cell Biology - May 5, 2019 Category: Cytology Authors: Goel, P., Dufour Bergeron, D., Böhme, M. A., Nunnelly, L., Lehmann, M., Buser, C., Walter, A. M., Sigrist, S. J., Dickman, D. Tags: Cell Signaling, Neuroscience, Physiology Articles Source Type: research
MACF1 links Rapsyn to microtubule- and actin-binding proteins to maintain neuromuscular synapses
Complex mechanisms are required to form neuromuscular synapses, direct their subsequent maturation, and maintain the synapse throughout life. Transcriptional and post-translational pathways play important roles in synaptic differentiation and direct the accumulation of the neurotransmitter receptors, acetylcholine receptors (AChRs), to the postsynaptic membrane, ensuring for reliable synaptic transmission. Rapsyn, an intracellular peripheral membrane protein that binds AChRs, is essential for synaptic differentiation, but how Rapsyn acts is poorly understood. We screened for proteins that coisolate with AChRs in a Rapsyn-d...
Source: Journal of Cell Biology - May 5, 2019 Category: Cytology Authors: Oury, J., Liu, Y., Töpf, A., Todorovic, S., Hoedt, E., Preethish-Kumar, V., Neubert, T. A., Lin, W., Lochmüller, H., Burden, S. J. Tags: Disease, Cytoskeleton, Neuroscience Articles Source Type: research
Tks5 and Dynamin-2 enhance actin bundle rigidity in invadosomes to promote myoblast fusion
Skeletal muscle development requires the cell–cell fusion of differentiated myoblasts to form muscle fibers. The actin cytoskeleton is known to be the main driving force for myoblast fusion; however, how actin is organized to direct intercellular fusion remains unclear. Here we show that an actin- and dynamin-2–enriched protrusive structure, the invadosome, is required for the fusion process of myogenesis. Upon differentiation, myoblasts acquire the ability to form invadosomes through isoform switching of a critical invadosome scaffold protein, Tks5. Tks5 directly interacts with and recruits dynamin-2 to the in...
Source: Journal of Cell Biology - May 5, 2019 Category: Cytology Authors: Chuang, M.-C., Lin, S.-S., Ohniwa, R. L., Lee, G.-H., Su, Y.-A., Chang, Y.-C., Tang, M.-J., Liu, Y.-W. Tags: Cytoskeleton, Biochemistry, Biophysics Articles Source Type: research
Drosophila FGF cleavage is required for efficient intracellular sorting and intercellular dispersal
How morphogenetic signals are prepared for intercellular dispersal and signaling is fundamental to the understanding of tissue morphogenesis. We discovered an intracellular mechanism that prepares Drosophila melanogaster FGF Branchless (Bnl) for cytoneme-mediated intercellular dispersal during the development of the larval Air-Sac-Primordium (ASP). Wing-disc cells express Bnl as a proprotein that is cleaved by Furin1 in the Golgi. Truncated Bnl sorts asymmetrically to the basal surface, where it is received by cytonemes that extend from the recipient ASP cells. Uncleavable mutant Bnl has signaling activity but is mistarget...
Source: Journal of Cell Biology - May 5, 2019 Category: Cytology Authors: Sohr, A., Du, L., Wang, R., Lin, L., Roy, S. Tags: Cell Signaling, Development Articles Source Type: research
ATG9A shapes the forming autophagosome through Arfaptin 2 and phosphatidylinositol 4-kinase III{beta}
ATG9A is a multispanning membrane protein essential for autophagy. Normally resident in Golgi membranes and endosomes, during amino acid starvation, ATG9A traffics to sites of autophagosome formation. ATG9A is not incorporated into autophagosomes but is proposed to supply so-far-unidentified proteins and lipids to the autophagosome. To address this function of ATG9A, a quantitative analysis of ATG9A-positive compartments immunoisolated from amino acid–starved cells was performed. These ATG9A vesicles are depleted of Golgi proteins and enriched in BAR-domain containing proteins, Arfaptins, and phosphoinositide-metabol...
Source: Journal of Cell Biology - May 5, 2019 Category: Cytology Authors: Judith, D., Jefferies, H. B. J., Boeing, S., Frith, D., Snijders, A. P., Tooze, S. A. Tags: Cell Death and Autophagy, Trafficking, Biochemistry Articles Source Type: research
CRACR2a is a calcium-activated dynein adaptor protein that regulates endocytic traffic
Cytoplasmic dynein is a minus end–directed microtubule motor that transports intracellular cargoes. Transport is initiated by coiled-coil adaptors that (a) join dynein and its cofactor dynactin into a motile complex and (b) interact with a cargo-bound receptor, which is frequently a Rab GTPase on an organelle. Here, we report two novel dynein adaptors, CRACR2a and Rab45, that have a coiled-coil adaptor domain, a pair of EF-hands, and a Rab GTPase fused into a single polypeptide. CRACR2a-mediated, but not Rab45-mediated, dynein motility is activated by calcium in vitro. In Jurkat T cells, elevation of intracellular ca...
Source: Journal of Cell Biology - May 5, 2019 Category: Cytology Authors: Wang, Y., Huynh, W., Skokan, T. D., Lu, W., Weiss, A., Vale, R. D. Tags: Cytoskeleton, Trafficking, Biochemistry Articles Source Type: research
Visualization of secretory cargo transport within the Golgi apparatus
In this study, we conducted simultaneous three-color and four-dimensional visualization of secretory transmembrane cargo together with early and late Golgi resident proteins. We show that cargo stays in a Golgi cisterna during maturation from cis-Golgi to trans-Golgi and further to the trans-Golgi network (TGN), which involves dynamic mixing and segregation of two zones of the earlier and later Golgi resident proteins. The location of cargo changes from the early to the late zone within the cisterna during the progression of maturation. In addition, cargo shows an interesting behavior during the maturation to the TGN. Afte...
Source: Journal of Cell Biology - May 5, 2019 Category: Cytology Authors: Kurokawa, K., Osakada, H., Kojidani, T., Waga, M., Suda, Y., Asakawa, H., Haraguchi, T., Nakano, A. Tags: Organelles, Trafficking Articles Source Type: research
Maturation-driven transport and AP-1-dependent recycling of a secretory cargo in the Golgi
Golgi cisternal maturation has been visualized by fluorescence imaging of individual cisternae in the yeast Saccharomyces cerevisiae, but those experiments did not track passage of a secretory cargo. The expectation is that a secretory cargo will be continuously present within maturing cisternae as resident Golgi proteins arrive and depart. We tested this idea using a regulatable fluorescent secretory cargo that forms ER-localized aggregates, which dissociate into tetramers upon addition of a ligand. The solubilized tetramers rapidly exit the ER and then transit through early and late Golgi compartments before being secret...
Source: Journal of Cell Biology - May 5, 2019 Category: Cytology Authors: Casler, J. C., Papanikou, E., Barrero, J. J., Glick, B. S. Tags: Organelles, Trafficking Articles Source Type: research
