MBoC Molecular Biology of the Cell Published by the American Society for Cell Biology Contents Perspective The Institute for the Study of Non–Model Organisms and other fantasies W. Sullivan 387–389 Articles Biosynthesis and Biodegradation Reglucosylation by UDP-glucose:glycoprotein glucosyltransferase 1 delays glycoprotein secretion but not degradation A. Tannous, N. Patel, T. Tamura, and D. N. Hebert The ER quality control factor UDP-glucose:glycoprotein glucosyltransferase 1 modifies folding intermediates but most efficiently terminally misfolded targets. Whereas on-pathway targets are retained in the ER when trapped in monoglucosylated states, off-pathway proteins are degraded rapidly, exposing a dominant ERAD selection process. 390–405 Cell Biology of Disease Methionine sulfoxide reductase 2 reversibly regulates Mge1, a cochaperone of mitochondrial Hsp70, during oxidative stress P. K. Allu, A. Marada, Y. Boggula, S. Karri, T. Krishnamoorthy, and N. B. V. Sepuri Methionine sulfoxide reductases are important regulators of oxidative stress, as they reduce oxidized methionine in proteins. Mge1, a cochaperone of mtHsp70, is a physiological substrate of Mxr2 and regulates reversibly to maintain mitochondrial protein homeostasis and oxidative stress. Sil1, a nucleotide exchange factor for BiP, is not required for antibody assembly or secretion V. P. Ichhaporia, T. Sanford, J. Howes, T. N. Marion, and L. M. Hendershot Sil1 is a nucleotide exchange factor for the ER chaperone BiP, and mutations in this gene lead to Marinesco–Sjögren syndrome, a multisystem disorder. Effects of loss of Sil1 on biosynthesis and secretion of antibodies, a well-characterized BiP client, are determined in a mouse model for this disease and patient-derived lymphoblastoid cell lines. 406–419 420–429 Transcriptional factor specificity protein 1 (SP1) promotes the proliferation of glioma cells by up-regulating midkine (MDK) Jingyan Luo, Xiaoxiao Wang, Zhibo Xia, Lixuan Yang, Zhiming Ding, Shiyuan Chen, Bingquan Lai, and Nu Zhang Midkine (MDK) expression is associated with the proliferation of many cancers, including glioma. SP1 directly up-regulates the expression of MDK, and the SP1-MDK axis cooperates in glioma tumorigenesis. 430–439 Cell Cycle A unique insertion in STARD9’s motor domain regulates its stability S. Senese, K. Cheung, Yu-Chen Lo, A. A. Gholkar, Xiaoyu Xia, J. A. Wohlschlegel, and J. Z. Torres A unique insertion in STARD9’s motor domain is phosphorylated by mitotic kinases, including Plk1, which regulate its levels through an SCFb-TrCP ubiquitin ligase and proteasome-dependent process. These results imply that in vivo, full-length STARD9 could be regulated by Plk1 and SCFβ-TrCP to promote proper mitotic spindle assembly. Regulation of Rho-GEF Rgf3 by the arrestin Art1 in fission yeast cytokinesis R. Davidson, D. Laporte, and Jian-Qiu Wu The arrestin Art1 and the Rho1 guanine nucleotide exchange factor Rgf3 are interdependent for their localizations to the division site during fission yeast cytokinesis. Art1 physically interacts with Rgf3 to modulate active Rho1 GTPase levels for successful septal formation. Volume 26 February 1, 2015 440–452 453–466 Cell Motility The formin FMNL3 assembles plasma membrane protrusions that participate in cell–cell adhesion T. J. Gauvin, L. E. Young, and H. N. Higgs FMNL3 localizes broadly over the plasma membrane as discrete puncta, with particular enrichment in filopodia and ruffles and at cell–cell contacts. In addition, a population of FMNL3-containing vesicles of endocytic origin can fuse with the plasma membrane. FMNL3 suppression causes reductions in filopodia and cell–cell adhesion. 467–477 Cytoskeleton Kinesin-13 regulates the quantity and quality of tubulin inside cilia K. K. Vasudevan, Yu-Yang Jiang, K. F. Lechtreck, Y. Kushida, L. M. Alford, W. S. Sale, T. Hennessey, and J. Gaertig Kinesin-13, a microtubule-end depolymerase, has been shown to affect the length of cilia, but its ciliary function is unclear. In Tetrahymena thermophila, kinesin-13 positively regulates the axoneme length, influences the properties of ciliary tubulin, and affects the ciliary dynein-dependent motility. A novel role for WAVE1 in controlling actin network growth rate and architecture M. O. Sweeney, A. Collins, S. B. Padrick, and B. L. Goode A novel functional role for WAVE1 is found that is lacking in N-WASP and WAVE2. Through its unique WH2 domain, WAVE1 dramatically reduces the rate of actin filament elongation independently of its interactions with the Arp2/3 complex. These findings help explain how cells build actin networks with distinct geometries and growth rates. 478–494 495–505 Membrane Trafficking Phospholipase D1 facilitates second-phase myoblast fusion and skeletal muscle regeneration Shuzhi Teng, D. Stegner, Qin Chen, T. Hongu, H. Hasegawa, Li Chen, Y. Kanaho, B. Nieswandt, M. A. Frohman, and Ping Huang Phospholipase D1 and its product, phosphatidic acid, facilitate muscle fiber regeneration in vivo and are required by mononuclear myocytes to fuse with nascent myotubes during second-phase myoblast fusion in vitro. Macrophages phagocytose nonopsonized silica particles using a unique microtubule-dependent pathway R. M. Gilberti and D. A. Knecht Cells can take up particles by both opsonized and nonopsonized pathways. Silica and latex, but not zymosan, can be taken up by the nonopsonized pathway. Uptake of silica, but not latex, is toxic to macrophages. Nonopsonized phagocytosis is characterized and found to have key differences from the complement- and antibody-opsonized pathways. A Highlights from MBoC Selection Characterization of VAMP isoforms in 3T3-L1 adipocytes: implications for GLUT4 trafficking J. B. A. Sadler, N. J. Bryant, and G. W. Gould The levels of expression, distribution, and association of all of the VAMPs expressed in 3T3-L1 adipocytes are characterized. This is the first systematic analysis of all members of this protein family for any cell type. A Highlights from MBoC Selection Coupling of vesicle tethering and Rab binding is required for in vivo functionality of the golgin GMAP-210 K. Sato, P. Roboti, A. A. Mironov, and M. Lowe Vesicle tethering mediated by the golgin GMAP-210 is required to maintain the structure of the Golgi apparatus. Tethering by GMAP-210 is mediated solely by the ALPS motif, and binding to Rab2 and the length of GMAP-210, although not required for tethering per se, are also critical for its functional role at the Golgi apparatus. Constitutively active ESCRT-II suppresses the MVB-sorting phenotype of ESCRT-0 and ESCRT-I mutants S. K. Mageswaran, N. K. Johnson, G. Odorizzi, and M. Babst This study is a step toward understanding the minimal requirements for MVB biogenesis and for ESCRT machinery in this process. Early ESCRT complexes (ESCRT-0 and -I) seem to have redundant functions in cargo sorting. Furthermore, vesicle formation seems to require cargo sorting in addition to late ESCRT machinery. 506–517 518–529 530–536 537–553 554–568 Signaling PAS kinase is activated by direct SNF1-dependent phosphorylation and mediates inhibition of TORC1 through the phosphorylation and activation of Pbp1 D. DeMille, B. D. Badal, J. B. Evans, A. D. Mathis, J. F. Anderson, and J. H. Grose The interplay between AMPK, Psk1, and TORC1 reduces cell growth and proliferation when energy is low. This interplay occurs through Snf1-dependent activation of Psk1, followed by phosphorylation of poly(A)-binding protein binding protein 1 (Pbp1) and subsequent inhibitory sequestration of TORC1 to stress granules. 569–582 Systems Biology Single-cell variation leads to population invariance in NF-κB signaling dynamics J. J. Hughey, M. V. Gutschow, B. T. Bajar, and M. W. Covert Most features of NF-κB activation dynamics vary significantly with respect to ligand type and concentration. The distribution of the time between two nuclear entries is an invariant feature in populations but not individual cells, suggesting an additional level of control, which regulates the overall distribution of translocation timing. 583–590
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