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Xuefei Zhang, Yanlin Li, Changhong Liu, Weifeng Wang, Mo Li, Desheng Lv, Ge Sun, Hui Chen, Xiaowei Dong, Zhibo Miao, Ming Yao, Kai Wang, Hui Tian
RET fusions have been reported in 1-2% of lung adenocarcinomas, and represent an actionable target. Patients whose tumors possess RET fusion are associated with clinical benefit from the treatment with multi-kinase inhibitors such as cabozantinib and vandetanib. Further molecular screening for RET fusions is warranted. Novel KIF13A-RET fusion containing an intact RET kinase domain involving exons 1-18 of KIF13A and exons 12-20 of RET was identified in a lung cancer specimen from an 74-year-old Asian never smoker by next-generation sequencing (NGS) during clinical care...
April 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
Xiaofan Xu, Mingming Pan, Alexis E Gasiewicz, Rongzi Li, Shiu-Ming Kuo
MDCK cells are widely used to study the differential targeting of membrane transporters to apical and basolateral membrane but its canine origin limited the commercial tools available for the analysis of protein trafficking machinery. Because apical and basolateral membranes are only found in differentiated epithelial cells, genes critical for differential targeting may be specifically up-regulated upon MDCK cell differentiation. To search for these genes, a cross-species screening strategy was used. We first analyzed the human microarray data for protein trafficking-related genes that were up-regulated in colon carcinoma Caco2 cells upon differentiation...
June 2017: Biochimie Open
Cécile Campagne, Léa Ripoll, Floriane Gilles-Marsens, Graça Raposo, Cédric Delevoye
Melanocytes are specialized cells that generate unique organelles called melanosomes in which melanin is synthesized and stored. Melanosome biogenesis and melanocyte pigmentation require the transport and delivery of melanin synthesizing enzymes, such as tyrosinase and related proteins (e.g., TYRP1), from endosomes to maturing melanosomes. Among the proteins controlling endosome-melanosome transport, AP-1 together with KIF13A coordinates the endosomal sorting and trafficking of TYRP1 to melanosomes. We identify here β1-adaptin AP-1 subunit-derived peptides of 5 amino acids that block the interaction of KIF13A with AP-1 in cells...
February 14, 2018: International Journal of Molecular Sciences
(no author information available yet)
First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping early-career researchers promote themselves alongside their papers. Ana Nascimento is the first author on 'KIF13A mediates trafficking of influenza A virus ribonucleoproteins', published in Journal of Cell Science. Ana conducted the work in this article in Maria João Amorim's lab at the Instituto Gulbenkian de Ciência, Portugal. She is now a PhD student in the lab of Beate Sodeik at the Institute of Virology at Hannover Medical School, investigating host-pathogen interactions, particularly involving viruses...
December 1, 2017: Journal of Cell Science
Ana Ramos-Nascimento, Bárbara Kellen, Filipe Ferreira, Marta Alenquer, Sílvia Vale-Costa, Graça Raposo, Cédric Delevoye, Maria João Amorim
Influenza A is a rapidly evolving virus that is successful in provoking periodic epidemics and occasional pandemics in humans. Viral assembly is complex as the virus incorporates an eight-partite genome of RNA (in the form of viral ribonucleoproteins, vRNPs), and viral genome assembly - with its implications to public health - is not completely understood. It has previously been reported that vRNPs are transported to the cell surface on Rab11-containing vesicles by using microtubules but, so far, no molecular motor has been assigned to the process...
December 1, 2017: Journal of Cell Science
Khawaja Ashfaque Ahmed, Jim Xiang
Mannose-6-phosphate receptor (M6PR) that facilitates cellular uptake of M6P-bearing proteins, including serine-protease granzyme-B (Gzm-B) has an important role in T-cell activation, migration and contraction. However, molecular mechanisms controlling M6PR expression in T cells remain poorly understood. Here, we show that M6PR expression on T cells is distinctively controlled by two common γ-chain cytokines interleukin-2 (IL-2) and IL-7, and the differential M6PR expression is not caused by an altered synthesis of M6PR protein, but is a result of distinct regulation of kinesin-3 motor-protein KIF13A that transport M6PR onto cell surfaces...
2017: Cell Discovery
Cédric Delevoye, Xavier Heiligenstein, Léa Ripoll, Floriane Gilles-Marsens, Megan K Dennis, Ricardo A Linares, Laura Derman, Avanti Gokhale, Etienne Morel, Victor Faundez, Michael S Marks, Graça Raposo
Recycling endosomes consist of a tubular network that emerges from vacuolar sorting endosomes and diverts cargoes toward the cell surface, the Golgi, or lysosome-related organelles. How recycling tubules are formed remains unknown. We show that recycling endosome biogenesis requires the protein complex BLOC-1. Mutations in BLOC-1 subunits underlie an inherited disorder characterized by albinism, the Hermansky-Pudlak Syndrome, and are associated with schizophrenia risk. We show here that BLOC-1 coordinates the kinesin KIF13A-dependent pulling of endosomal tubules along microtubules to the Annexin A2/actin-dependent stabilization and detachment of recycling tubules...
January 11, 2016: Current Biology: CB
Jinqi Ren, Lin Huo, Wenjuan Wang, Yong Zhang, Wei Li, Jizhong Lou, Tao Xu, Wei Feng
Processive kinesin motors often contain a coiled-coil neck that controls the directionality and processivity. However, the neck coil (NC) of kinesin-3 is too short to form a stable coiled-coil dimer. Here, we found that the coiled-coil (CC1)-forkhead-associated (FHA) tandem (that is connected to NC by Pro-390) of kinesin-3 KIF13A assembles as an extended dimer. With the removal of Pro-390, the NC-CC1 tandem of KIF13A unexpectedly forms a continuous coiled-coil dimer that can be well aligned into the CC1-FHA dimer...
February 12, 2016: Journal of Biological Chemistry
Marvin Bentley, Helena Decker, Julie Luisi, Gary Banker
Identifying the proteins that regulate vesicle trafficking is a fundamental problem in cell biology. In this paper, we introduce a new assay that involves the expression of an FKBP12-rapamycin-binding domain-tagged candidate vesicle-binding protein, which can be inducibly linked to dynein or kinesin. Vesicles can be labeled by any convenient method. If the candidate protein binds the labeled vesicles, addition of the linker drug results in a predictable, highly distinctive change in vesicle localization. This assay generates robust and easily interpretable results that provide direct experimental evidence of binding between a candidate protein and the vesicle population of interest...
February 2, 2015: Journal of Cell Biology
Virupakshi Soppina, Stephen R Norris, Aslan S Dizaji, Matt Kortus, Sarah Veatch, Michelle Peckham, Kristen J Verhey
The kinesin-3 family is one of the largest among the kinesin superfamily and its members play important roles in a wide range of cellular transport activities, yet the molecular mechanisms of kinesin-3 regulation and cargo transport are largely unknown. We performed a comprehensive analysis of mammalian kinesin-3 motors from three different subfamilies (KIF1, KIF13, and KIF16). Using Forster resonance energy transfer microscopy in live cells, we show for the first time to our knowledge that KIF16B motors undergo cargo-mediated dimerization...
April 15, 2014: Proceedings of the National Academy of Sciences of the United States of America
Cédric Delevoye, Stéphanie Miserey-Lenkei, Guillaume Montagnac, Floriane Gilles-Marsens, Perrine Paul-Gilloteaux, Francesca Giordano, François Waharte, Michael S Marks, Bruno Goud, Graça Raposo
Early endosomes consist of vacuolar sorting and tubular recycling domains that segregate components fated for degradation in lysosomes or reuse by recycling to the plasma membrane or Golgi. The tubular transport intermediates that constitute recycling endosomes function in cell polarity, migration, and cytokinesis. Endosomal tubulation and fission require both actin and intact microtubules, but although factors that stabilize recycling endosomal tubules have been identified, those required for tubule generation from vacuolar sorting endosomes (SEs) remain unknown...
February 13, 2014: Cell Reports
Julian P Venables, Laure Lapasset, Gilles Gadea, Philippe Fort, Roscoe Klinck, Manuel Irimia, Emmanuel Vignal, Philippe Thibault, Panagiotis Prinos, Benoit Chabot, Sherif Abou Elela, Pierre Roux, Jean-Marc Lemaitre, Jamal Tazi
Reprogramming somatic cells into induced pluripotent stem cells (iPSCs) has provided huge insight into the pathways, mechanisms and transcription factors that control differentiation. Here we use high-throughput RT-PCR technology to take a snapshot of splicing changes in the full spectrum of high- and low-expressed genes during induction of fibroblasts, from several donors, into iPSCs and their subsequent redifferentiation. We uncover a programme of concerted alternative splicing changes involved in late mesoderm differentiation and controlled by key splicing regulators MBNL1 and RBFOX2...
2013: Nature Communications
Ruyun Zhou, Shinsuke Niwa, Laurent Guillaud, Ying Tong, Nobutaka Hirokawa
Molecular motors are fundamental to neuronal morphogenesis and function. However, the extent to which molecular motors are involved in higher brain functions remains largely unknown. In this study, we show that mice deficient in the kinesin family motor protein KIF13A (Kif13a(-/-) mice) exhibit elevated anxiety-related behavioral phenotypes, probably because of a reduction in 5HT(1A) receptor (5HT(1A)R) transport. The cell-surface expression level of the 5HT(1A)R was reduced in KIF13A-knockdown neuroblastoma cells and Kif13a(-/-) hippocampal neurons...
February 21, 2013: Cell Reports
Sarah Katharina Fehling, Takeshi Noda, Andrea Maisner, Boris Lamp, Karl-Klaus Conzelmann, Yoshihiro Kawaoka, Hans-Dieter Klenk, Wolfgang Garten, Thomas Strecker
The small matrix protein Z of arenaviruses has been identified as the main driving force to promote viral particle production at the plasma membrane. Although multiple functions of Z in the arenaviral life cycle have been uncovered, the mechanism of intracellular transport of Z to the site of virus budding is poorly understood and cellular motor proteins that mediate Z trafficking remain to be identified. In the present study, we report that the Z protein of the Old World arenavirus Lassa virus (LASV) interacts with the kinesin family member 13A (KIF13A), a plus-end-directed microtubule-dependent motor protein...
February 2013: Cellular Microbiology
Brian Jenkins, Helena Decker, Marvin Bentley, Julie Luisi, Gary Banker
Identifying the kinesin motors that interact with different vesicle populations is a longstanding and challenging problem with implications for many aspects of cell biology. Here we introduce a new live-cell assay to assess kinesin-vesicle interactions and use it to identify kinesins that bind to vesicles undergoing dendrite-selective transport in cultured hippocampal neurons. We prepared a library of "split kinesins," comprising an axon-selective kinesin motor domain and a series of kinesin tail domains that can attach to their native vesicles; when the split kinesins were assembled by chemical dimerization, bound vesicles were misdirected into the axon...
August 20, 2012: Journal of Cell Biology
Tanja Maritzen, Volker Haucke
Different types of endosomal vesicles show distinct distribution patterns within cells. While early endosomes can be found throughout the cell, recycling endosomal vesicles and tubules tend to cluster near the microtubule organizing center in the perinuclear region in most cell types. The molecular mechanisms underlying the steady-state distribution and dynamics of various types of endosomal vesicles has long remained enigmatic. However, during the past decade it has become evident that microtubule-based motor proteins of the kinesin family play a pivotal role in the positioning of endosomes...
July 2010: Communicative & Integrative Biology
Rikke I Thorsteinsson, Søren T Christensen, Lotte B Pedersen
Most cells in our body form a single primary cilium when entering growth arrest. During the past decade, a number of studies have revealed a key role for primary cilia in coordinating a variety of signaling pathways that control important cellular and developmental processes. Consequently, significant effort has been directed toward the identification of genes involved in ciliary assembly and function. Many candidate ciliary genes and proteins have been identified using large-scale "omics" approaches, including proteomics, transcriptomics, and comparative genomics...
2009: Methods in Cell Biology
Antonia P Sagona, Ioannis P Nezis, Nina Marie Pedersen, Knut Liestøl, John Poulton, Tor Erik Rusten, Rolf I Skotheim, Camilla Raiborg, Harald Stenmark
Several subunits of the class III phosphatidylinositol-3-OH kinase (PI(3)K-III) complex are known as tumour suppressors. Here we uncover a function for this complex and its catalytic product phosphatidylinositol-3-phosphate (PtdIns(3)P) in cytokinesis. We show that PtdIns(3)P localizes to the midbody during cytokinesis and recruits a centrosomal protein, FYVE-CENT (ZFYVE26), and its binding partner TTC19, which in turn interacts with CHMP4B, an endosomal sorting complex required for transport (ESCRT)-III subunit implicated in the abscission step of cytokinesis...
April 2010: Nature Cell Biology
Cédric Delevoye, Ilse Hurbain, Danièle Tenza, Jean-Baptiste Sibarita, Stéphanie Uzan-Gafsou, Hiroshi Ohno, Willie J C Geerts, Arie J Verkleij, Jean Salamero, Michael S Marks, Graça Raposo
Specialized cell types exploit endosomal trafficking to deliver protein cargoes to cell type-specific lysosome-related organelles (LROs), but how endosomes are specified for this function is not known. In this study, we show that the clathrin adaptor AP-1 and the kinesin motor KIF13A together create peripheral recycling endosomal subdomains in melanocytes required for cargo delivery to maturing melanosomes. In cells depleted of AP-1 or KIF13A, a subpopulation of recycling endosomes redistributes to pericentriolar clusters, resulting in sequestration of melanosomal enzymes like Tyrp1 in vacuolar endosomes and consequent inhibition of melanin synthesis and melanosome maturation...
October 19, 2009: Journal of Cell Biology
Aparna Lakkaraju, Jose Maria Carvajal-Gonzalez, Enrique Rodriguez-Boulan
The role of clathrin adaptor proteins in sorting cargo in the biosynthetic and recycling routes is an area of intense research. In this issue, Delevoye et al. (2009. J. Cell Biol. doi:10.1083/jcb.200907122) show that a close interaction between the clathrin adaptor AP-1 and a kinesin motor KIF13A is essential for delivering melanogenic enzymes from recycling endosomes to nascent melanosomes and for organelle biogenesis.
October 19, 2009: Journal of Cell Biology
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