Molecular Biology of the Cell (MOL BIOL CELL )

Publisher: American Society for Cell Biology, American Society for Cell Biology

Journal description

Molecular Biology of the Cell, the journal owned and published by The American Society for Cell Biology, publishes papers that describe and interpret results of original research concerning the molecular aspects of cell structure and function. Studies whose scope bridges several areas of biology are particularly encouraged, for example cell biology and genetics. The aim of the Journal is to publish papers describing substantial research progress in full: papers should include all previously unpublished data and methods essential to support the conclusions drawn.

Current impact factor: 4.55

Impact Factor Rankings

2015 Impact Factor Available summer 2015
2013 / 2014 Impact Factor 4.548
2012 Impact Factor 4.604
2011 Impact Factor 4.942
2010 Impact Factor 5.861
2009 Impact Factor 5.979
2008 Impact Factor 5.558
2006 Impact Factor 6.562
2005 Impact Factor 6.52
2004 Impact Factor 7.517
2003 Impact Factor 7.454
2002 Impact Factor 7.599
2001 Impact Factor 7.7
2000 Impact Factor 8.482
1999 Impact Factor 7.527
1998 Impact Factor 8.256
1997 Impact Factor 8.926
1996 Impact Factor 9.915
1995 Impact Factor 9.376
1994 Impact Factor 10.051
1993 Impact Factor 9.025

Impact factor over time

Impact factor
Year

Additional details

5-year impact 5.35
Cited half-life 7.40
Immediacy index 1.07
Eigenfactor 0.10
Article influence 2.58
Website Molecular Biology of the Cell website
Other titles Molecular biology of the cell, MBC
ISSN 1059-1524
OCLC 24486692
Material type Periodical, Internet resource
Document type Journal / Magazine / Newspaper, Internet Resource

Publisher details

American Society for Cell Biology

  • Pre-print
    • Author cannot archive a pre-print version
  • Post-print
    • Author cannot archive a post-print version
  • Conditions
    • On author's personal website or institutional repository
    • Publisher's version/PDF must be used
    • In Press version must not be used
    • Publisher copyright and source must be acknowledged with citation
    • Must link to publisher version
    • Creative Commons Attribution Non-Commerical Share Alike 3.0 License
    • Articles are placed in PubMed Central after 2 months by publisher
  • Classification
    ​ blue

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Calponin-related proteins are widely distributed among eukaryotes and involved in signaling and cytoskeletal regulation. Calponin-like (CLIK) repeat is an actin-binding motif found in the C-termini of vertebrate calponins. Although CLIK repeats stabilize actin filaments, other function of these actin-binding motifs is unknown. The Caenorhabditis elegans unc-87 gene encodes actin-binding proteins with seven CLIK repeats. UNC-87 stabilizes actin filaments and is essential for maintenance of sarcomeric actin filaments in striated muscle. Here, we show that two UNC-87 isoforms, UNC-87A and UNC-87B, are expressed in muscle and non-muscle cells in a tissue-specific manner by two independent promoters and exhibit quantitatively different effects on both actin and myosin. Both UNC-87A and UNC-87B have seven CLIK repeats, but UNC-87A has an extra N-terminal extension of ∼190 amino acids. Both UNC-87 isoforms bind to actin filaments and myosin to induce ATP-resistant actomyosin bundles and inhibit actomyosin motility. UNC-87A with an N-terminal extension binds to actin and myosin more strongly than UNC-87B. UNC-87B is associated with actin filaments in non-striated muscle in the somatic gonad, and an unc-87 mutation causes its excessive contraction that is dependent on myosin. These results strongly suggest that proteins with CLIK repeats function as a negative regulator of actomyosin contractility. © 2015 by The American Society for Cell Biology.
    Molecular Biology of the Cell 02/2015;
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    ABSTRACT: All known mechanisms of mitotic spindle orientation rely on astral microtubules. We report that even in their absence metaphase spindles in MDCK and HeLa cells are not randomly positioned within their x-z dimension, but preferentially adopt shallow β angles between spindle pole axis and substratum. The non-random spindle positioning was due to constraints imposed by the cell cortex in flat cells that drove spindles that were longer and/or wider than the cell's height into a tilted quasi- diagonal x-z position. In rounder cells, which are taller, fewer cortical constraints made the x-z spindle position more random. Re-establishment of astral microtubule mediated forces aligned the spindle poles with cortical cues parallel to the substratum in all cells. However, in flat cells they frequently caused spindle deformations. Similar deformations were apparent when confined spindles rotated from tilted to parallel positions while MDCK cells progressed from prometaphase to metaphase. The spindle disruptions caused the engagement of the Spindle Assembly Checkpoint. We propose that cell rounding serves to maintain spindle integrity during its positioning. © 2015 by The American Society for Cell Biology.
    Molecular Biology of the Cell 02/2015;
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    ABSTRACT: Understanding the mechanism underlying axon regeneration is of great practical importance to develop therapeutic treatment for traumatic brain and spinal cord injuries. Dramatic cytoskeleton reorganization occurs at the injury site, and microtubules have been implicated in the regeneration process. Previously we demonstrated that microtubule sliding by conventional kinesin (Kinesin-1) is required for initiation of neurite outgrowth in Drosophila embryonic neurons, and that sliding is developmentally down-regulated when neurite outgrowth is completed. Here we report that mechanical axotomy of Drosophila neurons in culture triggers axonal regeneration and regrowth. Regenerating neurons contain actively sliding microtubules; this sliding, like sliding during initial neurite outgrowth, is driven by Kinesin-1 and is required for axonal regeneration. The injury induces a fast spike of calcium, and depolymerization of microtubules near the injury site, and subsequent formation of local new microtubule arrays with mixed polarity. These events are required for reactivation of microtubule sliding at the initial stages of regeneration. Furthermore, c-Jun N-terminal kinase (JNK) pathway promotes regeneration by enhancing microtubule sliding in injured mature neurons. © 2015 by The American Society for Cell Biology.
    Molecular Biology of the Cell 02/2015;
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    ABSTRACT: PICK1 is a modular scaffold implicated in synaptic receptor trafficking, containing a PDZ domain, a BAR domain, and an acidic C-terminal tail (ACT). Analysis by small angle x-ray scattering suggests a structural model that places the receptor-binding site of the PDZ domain and membrane-binding surfaces of the BAR and PDZ domains adjacent to each other, on the concave side of the banana-shaped PICK1 dimer. In the model, the ACT of one subunit of the dimer interacts with the PDZ and BAR domains of the other subunit, possibly accounting for autoinhibition. Consistently, full-length PICK1 shows diffuse cytoplasmic localization, but it clusters on vesicle-like structures that colocalize with the trans-Golgi network marker TGN38 upon deletion of either the ACT or PDZ domain. This localization is driven by the BAR domain. Live-cell imaging further reveals that PICK1-associated vesicles undergo fast, non-directional motility, in an F-actin-dependent manner, but deleting the ACT dramatically reduces vesicle speed. Thus, the ACT links PICK1-associated vesicles to a motility factor, likely myosin, but contrary to previous reports PICK1 neither binds nor inhibits Arp2/3 complex. © 2015 by The American Society for Cell Biology.
    Molecular Biology of the Cell 02/2015;
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    ABSTRACT: Organelles of the endolysosomal system undergo multiple fission and fusion events to combine sorting of selected proteins to the vacuole with endosomal recycling. This sorting requires a consecutive remodeling of the organelle surface in the course of endosomal maturation. Here, we attempted to dissect the remodeling and fusion machinery on endosomes during the process of endocytosis. We therefore traced selected GFP-tagged endosomal proteins relative to exogenously added fluorescently labeled α-factor on its way from the plasma membrane to the vacuole. Our data reveal that the machinery of endosomal fusion and ESCRT proteins has a similar temporal localization on endosomes, while they precede the retromer cargo recognition complex. Neither deletion of retromer nor the fusion machinery with the vacuole affects this maturation process, though the kinetics seem to be delayed due to ESCRT deletion. Importantly, in strains lacking the active Rab7-like Ypt7 or the vacuolar SNARE fusion machinery, α-factor still proceeds to late endosomes with the same kinetics. This indicates that endosomal maturation is mainly controlled by the early endosomal fusion and remodeling machinery, but not the downstream Rab Ypt7 or the SNARE machinery. Our data thus provide an important further understanding of endosomal biogenesis in the context of cargo sorting. © 2015 by The American Society for Cell Biology.
    Molecular Biology of the Cell 02/2015;
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    ABSTRACT: Aquaporin-1 (AQP1) enables greatly enhanced water flux across plasma membranes. The cytosolic carboxy-terminus of AQP1 has two acidic motifs homologous to known carbonic anhydrase II (CAII) binding sequences. CAII colocalizes with AQP1 in the renal proximal tubule. Expression of AQP1 with CAII in Xenopus oocytes or mammalian cells increased water flux relative to AQP1 expression alone. This required the amino terminal sequence of CAII, a region that binds other transport proteins. Expression of catalytically-inactive CAII failed to increase water flux through AQP1. Proximity ligation assays revealed close association of CAII and AQP1, an effect requiring the second acidic cluster of AQP1. This motif was also necessary for CAII to increase AQP1-mediated water flux. Red blood cell ghosts resealed with CAII demonstrated increased osmotic water permeability compared with ghosts resealed with albumin. Water flux across renal cortical membrane vesicles, measured by stopped-flow light scattering, was reduced in CAII-deficient mice compared with wild-type mice. These data are consistent with CAII increasing water conductance through AQP1 by a physical interaction between the two proteins.
    Molecular Biology of the Cell 01/2015;
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    ABSTRACT: The receptor tyrosine kinase Axl has been described as an oncogene and its deregulation has been implicated in the progression of several human cancers. While the role of Axl in oesophageal adenocarcinoma has been addressed, there is no information about its role in oesophageal squamous cell carcinoma. In the current report, we identified, for the first time, deregulation of Axl expression in oesophageal squamous cell carcinoma (OSCC). Axl is consistently overexpressed in OSCC cell lines and human tumor samples, mainly in advanced stages of the disease. Blockage of Axl gene expression by small interfering RNA inhibits cell survival, proliferation, migration, and invasion in vitro and oesophageal tumor growth in vivo. Additionally, repression of Axl expression results in Akt-dependent inhibition of pivotal genes involved in the NF-κB pathway and in the induction of GSK3β activity, resulting in loss of mesenchymal and induction of epithelial markers. Furthermore, treatment of oesophageal cancer cells with the Akt inhibitor wortmannin inhibits NF-κB signaling, induces GSK3β activity and blocks OSCC cell proliferation in an Axl-dependent manner. Taken together, our results establish a clear role for Axl in OSCC tumorigenesis with potential therapeutic implications. © 2015 by The American Society for Cell Biology.
    Molecular Biology of the Cell 01/2015;
  • Molecular Biology of the Cell 01/2015;
  • Molecular Biology of the Cell 01/2015;
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    ABSTRACT: Kindlins are integrin interacting proteins, essential for integrin mediated cell adhesiveness. In this study, we focused on the evolutionary origin and functional specialization of Kindlins as a part of evolutionary adaptation of cell adhesive machinery. The database searches revealed that many members of integrin machinery (including Talin and integrins) already existed prior to Kindlin emergence in evolution. Among the analyzed species, all metazoan lineages-but none of the premetazoans-had at least one Kindlin encoding gene, whereas Talin was present in several premetazoan lineages. Kindlin appears to originate from a duplication of the sequence encoding the N-terminal fragment of Talin (the Talin Head domain), with a subsequent insertion of the PH domain of a separate origin. Sequence analysis identified a member of the Actin Filament-associated Protein 1 (AFAP1) superfamily as the most likely origin of the Kindlin PH domain. The functional divergence between Kindlin paralogs was assessed using the sequence swap (chimera) approach. Comparison of Kindlin 2 (K2)/Kindlin 3 (K3) chimeras revealed that the F2 subdomain, in particular its C-terminal part, is crucial for the differential functional properties of K2 and K3. The presence of this segment enables K2 but not K3 to localize to focal adhesions. Sequence analysis of the C-terminal part of the F2 subdomain of K3 suggests that an insertion of a variable glycine-rich sequence in vertebrates contributed to the loss of constitutive K3 targeting to focal adhesions. Thus, emergence and subsequent functional specialization of Kindlins allowed multicellular organisms to develop additional tissue-specific adaptations of cell adhesiveness. © 2014 by The American Society for Cell Biology.
    Molecular Biology of the Cell 12/2014;
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    ABSTRACT: Seipin is necessary both for adipogenesis and lipid droplet organization in non-adipose tissues, however its molecular function is incompletely understood. Phenotypes in the seipin-null mutant of Saccharomyces cerevisiae include aberrant droplet morphology (ER-droplet clusters and size heterogeneity) and sensitivity of droplet size to changes in phospholipid synthesis. It has not been clear, however, whether seipin acts in initiation of droplet synthesis or a later step. Here we utilize a system of de novo droplet formation to show that the absence of seipin results in a delay in droplet appearance with concomitant accumulation of neutral lipid in membranes. We also demonstrate that seipin is required for vectorial budding of droplets toward the cytoplasm. Furthermore, we find that the normal rate of droplet initiation depends on 14 amino acids at the amino terminus of seipin, deletion of which results in fewer, larger droplets that are consistent with a delay in initiation but are otherwise normal in morphology. Importantly, other functions of seipin, namely vectorial budding and resistance to inositol, are retained in this mutant. We conclude that seipin has dissectible roles in both promoting early lipid droplet initiation and in regulating lipid droplet morphology, supporting an important role in lipid droplet biogenesis. © 2014 by The American Society for Cell Biology.
    Molecular Biology of the Cell 12/2014;
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    ABSTRACT: Discoidin domain receptor 1 (DDR1) is a receptor tyrosine kinase that binds and transmits signals from various collagens in epithelial cells. However, how DDR1-dependent signaling is regulated has not been understood. Here we report that collagen binding induces ADAM10-dependent ectodomain shedding of DDR1. DDR1 shedding is not a result of an activation of its signaling pathway since DDR1 mutants defective in signaling were shed in an efficient manner. DDR1 and ADAM10 were found to be in a complex on the cell surface, but shedding did not occur unless collagen bound to DDR1. Using a shedding resistant DDR1 mutant, we found that ADAM10-dependent DDR1 shedding regulates the half-life of collagen-induced phosphorylation of the receptor. Our data also revealed that ADAM10 plays an important role in regulating DDR1 mediated cell adhesion to achieve efficient cell migration on collagen matrices. © 2014 by The American Society for Cell Biology.
    Molecular Biology of the Cell 12/2014;
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    ABSTRACT: Chromatin and nuclear pore complexes (NPCs) undergo dramatic changes during mitosis which in vertebrates and Aspergillus nidulans involves movement of Nup2 from NPCs to the chromatin region to fulfill unknown functions. This transition is shown to require the Cdk1 mitotic kinase and to be promoted prematurely by ectopic expression of the NIMA kinase. Nup2 localizes with a copurifying partner termed NupA, a highly divergent yet essential NPC protein. NupA and Nup2 locate throughout the chromatin region during prophase but during anaphase move to surround segregating DNA. NupA function is shown to involve targeting Nup2 to its interphase and mitotic locations. Deletion of either Nup2 or NupA causes identical mitotic defects that initiate a spindle assembly checkpoint (SAC) dependent mitotic delay and also cause defects in karyokinesis. These mitotic problems are not caused either by overall defects in mitotic NPC disassembly-reassembly or general nuclear import. However, without Nup2 or NupA, although the SAC protein Mad1 locates to its mitotic locations it fails to locate to NPCs normally in G1 after mitosis. Collectively the study provides new insight to the roles of Nup2 and NupA during mitosis and in a surveillance mechanism that regulates nucleokinesis when mitotic defects occur after SAC fulfillment. © 2014 by The American Society for Cell Biology.
    Molecular Biology of the Cell 12/2014;
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    ABSTRACT: The anaphase-promoting complex/cyclosome (APC/C) controls a variety of cellular processes through its ability to target numerous protein substrates for timely degradation. Substrate selection by this ubiquitin ligase depends on related activator proteins, Cdc20 and Cdh1, which bind and activate the APC/C at distinct cell cycle stages. Biochemical and structural studies revealed that Cdc20 and Cdh1 carry conserved receptor domains to recognize specific sequence motifs in substrates, such as d- and KEN-boxes. The mechanisms for ordered degradation of APC/C substrates, however, remain incompletely understood. Here, we describe minimal degradation sequences (degrons) sufficient for rapid APC/C-Cdh1-specific in vivo degradation. The polo kinase Cdc5-derived degron contained an essential KEN motif, while a single RxxL-type d-box was the relevant signal in the Cdc20-derived degradation domain, indicating that either motif may support specific recognition by Cdh1. In both degrons, the APC/C recognition motif was flanked by a nuclear localization sequence. Forced localization of the degron constructs revealed that proteolysis mediated by APC/C-Cdh1 is restricted to the nucleus and maximally active in the nucleoplasm. Levels of Iqg1, a cytoplasmic Cdh1 substrate, decreased detectably later than the nuclear-localized Cdh1 substrate Ase1, indicating that confinement to the nucleus may allow for temporal control of APC/C-Cdh1-mediated proteolysis. © 2014 by The American Society for Cell Biology.
    Molecular Biology of the Cell 12/2014;
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    ABSTRACT: DIF-1 is a polyketide that induces Dictyoselium amoebae to differentiate as prestalk cells. We performed a global quantitative screen for phosphorylation changes that occur within the first minutes after addition of DIF-1 using a triple-label SILAC approach. This revealed a new world of DIF-1 controlled signaling: with changes in components of the MAPK and protein kinase-B signaling pathways, components of the actinomyosin cytoskeletal signaling networks and in a broad range of small GTPases and their regulators. The results also provide evidence that the Ca(2+)/calmodulin dependent phosphatase calcineurin plays a role in DIF-1 signaling to the DimB prestalk transcription factor. At the global level DIF-1 causes a major shift in the phosphorylation/dephosphorylation equilibrium toward net dephosphorylation. Interestingly, many of the sites that are dephosphorylated in response to DIF-1 are phosphorylated in response to extracellular cAMP signaling. This accords with studies that suggest an antagonism between the two inducers and also with the rapid dephosphorylation of the cAMP receptor that we observe in response to DIF-1 and with the known inhibitory effect of DIF-1 on chemotaxis to cAMP. All MS data are available via ProteomeXchange with identifier PXD001555. © 2014 by The American Society for Cell Biology.
    Molecular Biology of the Cell 12/2014;
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    ABSTRACT: Transcriptional stochasticity can be measured by counting the number of mRNA molecules per cell. Cell-to-cell variability is best captured in terms of concentrations rather than molecule counts, because reaction rates depend on concentrations. We combined single-molecule mRNA counting with single-cell volume measurements to quantify the statistics of both transcript numbers and concentrations in human cells. We compare three cell clones that differ only in the genomic integration site of an identical constitutively expressed reporter gene. The transcript numbers per cell varied proportional with cell volume in all three clones, indicating concentration homeostasis. We find that the cell-to-cell variability in the mRNA concentration is almost exclusively due to cell-to-cell variation in gene expression activity, whereas the cell-to-cell variation in mRNA number is larger, due to a significant contribution of cell-volume variability. We conclude that the precise relationship between transcript numbers and cell volume sets the biological stochasticity of living cells. This study highlights the importance of the quantitative measurement of transcript concentrations in studies of cell-to-cell variability in biology. © 2014 by The American Society for Cell Biology.
    Molecular Biology of the Cell 12/2014;
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    ABSTRACT: Increased levels of hepatocyte growth factor (HGF) in the injured lungs may reflect compensatory response to diminish acute lung injury (ALI). HGF-induced activation of Rac1 GTPase stimulates endothelial barrier protective mechanisms. This study tested the involvement of Rac-specific guanine nucleotide exchange factor Asef in the HGF-induced endothelial cell (EC) cytoskeletal dynamics and barrier protection in vitro and in a two-hit model of ALI. HGF induced membrane translocation of Asef and stimulated Asef Rac1-specific nucleotide exchange activity. Expression of constitutively activated Asef mutant mimicked HGF-induced peripheral actin cytoskeleton enhancement. In contrast, siRNA-induced Asef knockdown or expression of dominant negative Asef attenuated HGF-induced Rac1 activation evaluated by Rac-GTP pulldown and FRET assay with Rac1 biosensor. Molecular inhibition of Asef attenuated HGF-induced peripheral accumulation of cortactin, formation of lamellipodia-like structures, enhancement of VE-cadherin adherens junctions and compromised HGF protective effect against thrombin-induced RhoA GTPase activation, Rho-dependent cytoskeleton remodeling and EC permeability. Intravenous HGF injection attenuated lung inflammation and vascular leak in the two-hit model of ALI induced by excessive mechanical ventilation and thrombin signaling peptide TRAP6. This effect was lost in Asef-/- mice. This study shows for the first time the role of Asef in HGF-mediated protection against endothelial hyperpermeability and lung injury. © 2014 by The American Society for Cell Biology.
    Molecular Biology of the Cell 12/2014;