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To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.cell.2010.10.003 Byline: Manojkumar A. Puthenveedu (1), Benjamin Lauffer (2), Paul Temkin (2), Rachel Vistein (1), Peter Carlton (3), Kurt Thorn (4), Jack Taunton (5), Orion D. Weiner (4), Robert G. Parton (6), Mark von Zastrow (2)(5) Keywords: CELLBIO; SIGNALING Abstract: The functional consequences of signaling receptor endocytosis are determined by the endosomal sorting of receptors between degradation and recycling pathways. How receptors recycle efficiently, in a sequence-dependent manner that is distinct from bulk membrane recycling, is not known. Here, in live cells, we visualize the sorting of a prototypical sequence-dependent recycling receptor, the beta-2 adrenergic receptor, from bulk recycling proteins and the degrading delta-opioid receptor. Our results reveal a remarkable diversity in recycling routes at the level of individual endosomes, and indicate that sequence-dependent recycling is an active process mediated by distinct endosomal subdomains distinct from those mediating bulk recycling. We identify a specialized subset of tubular microdomains on endosomes, stabilized by a highly localized but dynamic actin machinery, that mediate this sorting, and provide evidence that these actin-stabilized domains provide the physical basis for a two-step kinetic and affinity-based model for protein sorting into the sequence-dependent recycling pathway. Author Affiliation: (1) Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA, USA (2) Department of Psychiatry, University of California at San Francisco, San Francisco, CA 94158, USA (3) Department of Physiology, University of California at San Francisco, San Francisco, CA 94158, USA (4) Department of Biochemistry and Biophysics, University of California at San Francisco, San Francisco, CA 94158, USA (5) Department of Cellular and Molecular Pharmacology, University of California at San Francisco, San Francisco, CA 94158, USA (6) The University of Queensland, Institute for Molecular Bioscience and Centre for Microscopy and Microanalysis, St. Lucia, Queensland 4072, Australia 8 Article History: Received 31 October 2009; Revised 7 April 2010; Accepted 27 September 2010 Article Note: (miscellaneous) Published: November 24, 2010

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.cell.2006.09.034 Byline: Ramiro E. Verdun (1), Jan Karlseder (1) Abstract: Telomeres protect chromosome ends from being detected as lesions and from triggering DNA damage checkpoints. Paradoxically, telomere function depends on checkpoint proteins such as ATM and ATR, but a molecular model explaining this seemingly contradictory relationship has been missing so far. Here we show that the DNA damage machinery acts on telomeres in at least two independent steps. First, the ATR-dependent machinery is recruited to telomeres before telomere replication is completed, likely in response to single-stranded DNA resulting from replication fork stalling. Second, after replication, telomeres attract ATM and the homologous recombination (HR) machinery. In vivo and in vitro results suggest that the HR machinery is required for formation of a telomere-specific structure at chromosome ends after replication. Our results suggest that telomere ends need to be recognized as DNA damage to complete end replication and to acquire a structure that is essential for function. Author Affiliation: (1) The Salk Institute for Biological Studies, 10010 North Torrey Pines Rd., La Jolla, CA 92037, USA Article History: Received 30 May 2006; Revised 26 July 2006; Accepted 29 September 2006 Article Note: (miscellaneous) Published: November 16, 2006

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.cell.2006.02.044 Byline: Qian Wang (1), Junmin Pan (1), William J. Snell (1) Abstract: Primary cilia are widely used for signal transduction during development and in homeostasis and are assembled and maintained by intraflagellar transport (IFT). Here, we have dissected the role of IFT in signaling within the flagella (structural and functional counterparts of cilia) of the biflagellated green alga Chlamydomonas. Using a conditional IFT mutant enables us to deplete the IFT machinery from intact, existing flagella. We identify a cGMP-dependent protein kinase (CrPKG) within flagella as the substrate of a protein tyrosine kinase activated by flagellar adhesion during fertilization. We demonstrate that flagellar adhesion stimulates association of CrPKG with a new flagellar compartment. Moreover, formation of the compartment requires IFT, and IFT particles themselves are part of the compartment. Our results lead to a model in which the IFT machinery is required not only for assembling cilia and flagella but also for organizing a signaling pathway within the organelles during cilium-generated signaling. Author Affiliation: (1) Department of Cell Biology, University of Texas Southwestern Medical School, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA Article History: Received 9 August 2005; Revised 18 November 2005; Accepted 7 February 2006 Article Note: (miscellaneous) Published: May 4, 2006

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.cell.2005.04.036 Byline: Dawit Kidane, Peter L. Graumann Abstract: We have found that two DNA repair/recombination proteins localize differentially to the cell poles in competent Bacillus subtilis cells. RecA protein colocalized with competence protein ComGA, and its polar localization largely depended on ComGA and ComK activity, while RecN oscillated between the poles in a minute time frame, independent of any competence factor. Oscillation of RecN arrested upon addition of external DNA, suggesting that an interaction with incoming single-stranded (ss) DNA favors the localization of RecN at the pole containing the competence machinery. In agreement with this model, purified RecN protein showed ATP-dependent binding to ssDNA. Addition of DNA resulted in the formation of RecA threads emanating from the competence machinery. Our data show that in competent bacteria there exists a specifically positioned and dynamic ssDNA binding apparatus that accepts ssDNA taken up through the polar competence machinery and processes ssDNA for recombination with chromosomal DNA via extended RecA filaments. Author Affiliation: Institut fur Mikrobiologie, Fachbereich Biologie II, Universitat Freiburg, Verfugungsgebaude, Stefan-Meier-Str. 19, 79104 Freiburg, Germany Article History: Received 22 February 2005; Revised 15 April 2005; Accepted 23 April 2005 Article Note: (miscellaneous) Published: July 14, 2005