Highlights from MBoC

The Editorial Board of Molecular Biology of the Cell has highlighted the following articles from the November and December 2016 issues. From among the many fine articles in the journal, the Board selects for these Highlights articles that are of broad interest and significantly advance knowledge or provide new concepts or approaches that extend our understanding.

T lymphocytes in the human body routinely undergo large deformations, both passively when going through narrow capillaries and actively when transmigrating across endothelial cells or squeezing through tissue. In this artistic rendering, a T lymphocyte is aspirated in a micropipette to mimic passive deformations that occur when squeezing through narrow capillaries. The fluorescent signal is due to the entry of propidium iodide into the cell and indicates membrane rupture. Guillou et al. (Mol. Biol. Cell 27, 3574–3582) demonstrate that T lymphocytes rupture at a critical membrane area expansion when passively deformed. They further show that the unfolded membrane matches the excess membrane contained in microvilli and membrane folds. In contrast, during transendothelial migration, a form of active deformation, the authors find that the membrane surface exceeds by a factor of two the amount of membrane stored in microvilli and folds. (Image: by Julien Husson, Ecole polytechnique, Palaiseau, France; cellmechanics.jimdo.com/galleries)

Amyloid β-peptides interfere with mitochondrial preprotein import competence by a coaggregation process
Giovanna Cenini, Cornelia Rüb, Michael Bruderek, and Wolfgang Voos
Aggregation-prone amyloid β-peptides occurring in Alzheimer’s disease (AD) inhibit the import of nuclear-encoded mitochondrial precursor proteins. The observation of insoluble coaggregates between preproteins and Aβ peptides provides a biochemical explanation for mitochondrial dysfunction typically observed in AD-affected cells.
Mol. Biol. Cell 27 (21), 3257–3272

Membrane dynamics of dividing cells imaged by lattice light-sheet microscopy
François Aguet, Srigokul Upadhyayula, Raphaël Gaudin, Yi-ying Chou, Emanuele Cocucci, Kangmin He, Bi-Chang Chen, Kishore Mosaliganti, Mithun Pasham, Wesley Skillern, Wesley R. Legant, Tsung-Li Liu, Greg Findlay, Eric Marino, Gaudenz Danuser, Sean Megason, Eric Betzig, and Tom Kirchhausen
Lattice light-sheet microscopy is used to examine two problems in membrane dynamics—molecular events in clathrin-coated pit formation and changes in cell shape during cell division. This methodology sets a new standard for imaging membrane dynamics in single cells and multicellular assemblies.
Mol. Biol. Cell 27 (22), 3418–3435

Cell density and actomyosin contractility control the organization of migrating collectives within an epithelium
Andrew J. Loza, Sarita Koride, Gregory V. Schimizzi, Bo Li, Sean X. Sun, and Gregory D. Longmore
Cell density organizes collective migration within an epithelium. Computational models predict the regulation of collective migration in an in vivo epithelium and demonstrate how commonly altered cellular properties can prime groups of cells to adopt migration patterns that may be harnessed in health or exploited in disease.
Mol. Biol. Cell 27 (22), 3459–3470

T-lymphocyte passive deformation is controlled by unfolding of membrane surface reservoirs
Lionel Guillou, Avin Babataheri, Michael Saitakis, Armelle Bohineust, Stéphanie Dogniaux, Claire Hivroz, Abdul I. Barakat, and Julien Husson
T-lymphocyte passive deformation when squeezing through narrow capillaries is limited by the excess membrane contained in microvilli and membrane folds. During active processes such as transendothelial migration, larger deformations are made possible by an increase in membrane area, possibly through recruitment of internal membrane reservoirs.
Mol. Biol. Cell 27 (22), 3574–3582

Virtual-tissue computer simulations define the roles of cell adhesion and proliferation in the onset of kidney cystic disease
Julio M. Belmonte, Sherry G. Clendenon, Guilherme M. Oliveira, Maciej H. Swat, Evan V. Greene, Srividhya Jeyaraman, James A. Glazier, and Robert L. Bacallao
Virtual-tissue modeling is used to model emergent cyst growth in polycystic kidney disease. Model predictions, confirmed experimentally, show that decreased cell adhesion is necessary to produce stalk cysts, and loss of contact inhibition causes saccular cysts. Virtual-tissue modeling can be used to fully explore cell- and tissue-based behaviors.
Mol. Biol. Cell 27 (22), 3673–3685

Syndapin/SDPN-1 is required for endocytic recycling and endosomal actin association in the Caenorhabditis elegans intestine
Adenrele M. Gleason, Ken C.Q. Nguyen, David H. Hall, and Barth D. Grant
In vivo analysis of the F-BAR–domain protein syndapin indicates that it regulates basolateral recycling of transmembrane cargo in the Caenorhabditis elegans intestine. SDPN-1 may facilitate the fission of membranes from the early endosome that are acquiring recycling endosome characteristics, allowing cargo to exit the early endosome.
Mol. Biol. Cell 27 (23), 3746–3756

The poly(ADP-ribose)-dependent chromatin remodeler Alc1 induces local chromatin relaxation upon DNA damage
Hafida Sellou, Théo Lebeaupin, Catherine Chapuis, Rebecca Smith, Anna Hegele, Hari R. Singh, Marek Kozlowski, Sebastian Bultmann, Andreas G. Ladurner, Gyula Timinszky, and Sébastien Huet
PARP1 and its effector, the ATP-dependent chromatin remodeler Alc1/Chd1L, are identified as key players during the rapid chromatin relaxation at DNA damage sites.
Mol. Biol. Cell 27 (24), 3791–3799

Nebulette is a powerful cytolinker organizing desmin and actin in mouse hearts
Daniel A. Hernandez, Christina M. Bennett, Lyubov Dunina-Barkovskaya, Tatjana Wedig, Yassemi Capetanaki, Harald Herrmann, and Gloria M. Conover
Nebulette physically links desmin to sarcomeric actin in hearts. An intact desmin network is required for nebulette to function as major actin-binding protein in sarcomeres. This study provides biochemical evidence that the desmin–nebulette complex is involved in filament-forming desminopathy.
Mol. Biol. Cell 27 (24), 3869–3882

The phospholipid flippase ATP9A is required for the recycling pathway from the endosomes to the plasma membrane
Yoshiki Tanaka, Natsuki Ono, Takahiro Shima, Gaku Tanaka, Yohei Katoh, Kazuhisa Nakayama, Hiroyuki Takatsu, and Hye-Won Shin
ATP9A is localized to phosphatidylserine-positive early and recycling endosomes, but not late endosomes, in HeLa cells. ATP9A plays a crucial role in recycling of transferrin and glucose transporter 1 from endosomes to the plasma membrane.
Mol. Biol. Cell 27 (24), 3883–3893

The residue at position 5 of the N-terminal region of Src and Fyn modulates their myristoylation, palmitoylation, and membrane interactions
Efrat Gottlieb-Abraham, Orit Gutman, Govind M. Pai, Ignacio Rubio, and Yoav I. Henis
Using biophysical methods in live cells and palmitoylation mutants of Src and Fyn, we show that palmitoylation stabilizes the interactions of SFKs with the plasma membrane. Moreover, we show that the amino acid at position 5 regulates the myristoylation and palmitoylation of these proteins, and thereby their targeting to raft domains.
Mol. Biol. Cell 27 (24), 3926–3936

Lamin-B1 contributes to the proper timing of epicardial cell migration and function during embryonic heart development
Joseph R. Tran, Xiaobin Zheng, and Yixian Zheng
Lamin-B1 is important for the timing of cell morphological changes and migration of epicardial cells during embryogenesis. The results highlight the use of these cells for in vitro and in vivo study of these classic cell biological phenomena.
Mol. Biol. Cell 27 (25), 3956–3963

LTE1 promotes exit from mitosis by multiple mechanisms
Jill E. Falk, Ian W. Campbell, Kelsey Joyce, Jenna Whalen, Anupama Seshan, and Angelika Amon
In budding yeast, the spindle position checkpoint ensures that cells exit from mitosis only when their spindle is properly aligned along the mother–bud axis. Exit from mitosis is controlled by both negative signals in the mother cell compartment and positive signals in the bud.
Mol. Biol. Cell 27 (25), 3991–4001

Identification of the endocytic sorting signal recognized by the Art1-Rsp5 ubiquitin ligase complex
Evan L. Guiney, Till Klecker, and Scott D. Emr
Endocytosis of plasma membrane proteins in Saccharomyces cerevisiae requires their ubiquitination by the ART-Rsp5 ubiquitin ligase complex. Little is known about how the complex engages substrates. The Art1 C-terminus recognizes Mup1 via a tripartite ART sorting signal: an acidic patch, in proximity to the membrane and substrate lysines.
Mol. Biol. Cell 27 (25), 4043–4054

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