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Biological Sciences Department Faculty
Associate Professor, University of Toledo, Toledo, USA
Assistant Professor, Harvard Medical School, Boston, USA
Postdoc, University of California, San Diego, United States (Charles Zuker)
Ph.D. Weizmann Institute of Science, Rehovot, Israel (Zvi Vogel)
M.Sc. Hebrew University, Jerusalem, Israel (Daphne Atlas)
B.Sc. Hebrew University, Jerusalem, Israel
My research goal is to understand the mechanisms underlying centrosome biogenesis. Centrosomes are fundamental cellular components that are critical for human health. Defective centrosome biogenesis is associated with numerous types of cancer; it is also known to cause kidney disease, male infertility, and various developmental disorders, including Bardet-Biedl syndrome, left-right asymmetry, and microcephaly. Understanding normal centrosome biogenesis has been a fundamental Cell Biology question that has eluded researchers for over 120 years. To gain significant new insight in this area, we have developed a new and comprehensive approach for studying centrosome biogenesis. This approach combines genetics, biochemistry, molecular biology, bioinformatics, and light & electron microscopy.
- The centrosome consists of a pair of centrioles surrounded by an amorphous protein network of pericentriolar material (PCM). How a centrosome acquires its PCM is poorly understood. Here, we discovered a mechanism for PCM assembly (Gopalakrishnan, Nature Communications, 2011). We found that the centrosomal protein Sas-4 is responsible for PCM formation by scaffolding cytoplasmic complexes of PCM proteins and tethering them in the centrosome. This is the first clear demonstration that PCM complexes are prefabricated in the cytoplasm rather than each PCM protein being added to the centrosome individually. It also provided a mechanistic understanding of Sas-4 function.
- Following our initial work with Sas‑4 and its cytoplasmic complexes, we recently discovered how these complexes are regulated. Furthermore, we discovered that activation of these complexes leads to activation of the centrosome itself (Gopalakrishnan, Nature cell biology, 2012).
- Centrioles are conserved nine-fold symmetric organelles that reside at the center of a centrosome. The mechanisms ensuring the formation of centrioles with proper morphology have, to date, not been well characterized. It was speculated that a centriole’s morphology is determined by the morphology of the structure at its core (the Central Tubule) and that the Central Tubule’s morphology is determined by Sas‑6. In this project, we were the first to provide evidence in support of this idea (Gopalakrishnan, JBC, 2010). In particular, we discovered that Sas‑6 polymerize into central tubule-like structures. This data provided a mechanism by which Sas‑6 could be responsible for dictating the centrosome’s morphology.
- An animal cell requires precisely two centrioles; this number is maintained throughout an animal’s development by undergoing only one round of centriole duplication (of its two pre-existing centrioles) per cell cycle. The first cell in an animal’s development (i.e., the zygote) is likewise expected to have two centrioles. However, Drosophila oocyte’s (which lack centrioles) are thought to inherit only a single centriole from the sperm. In this project, we discovered a second centriolar structure in Drosophila sperm, the PCL (Blachon, Genetics, 2009). The PCL lacks the structural features that define a centriole, yet its initial formation uses the same genetic pathway used for centriole formation. From this, we reason that the PCL is a unique type of centriolar structure. Thus, the zygote appears to inherit two centriolar structures. Many questions relating to centriole inheritance (in Drosophila and mammals) remain unanswered. Our discovery of the PCL in Drosophila could explain centriolar inheritance in flies, and additionally, may provide insight into centriolar inheritance in other animals, including humans.
- In preparation for every cell division, a new centrosome forms. Centrosome formation is preceded by centriole duplication, a process that we know little about. We discovered a new allele of the centrosomal protein Asterless (Asl) and demonstrated that instead of being essential for centrosome function, as previously believed, Asl is essential early in centriole duplication (Blachon, Genetics, 2008). We showed that Asl is one of few centrosomal proteins essential for the initiation of centriole duplication; therefore, Asl is likely to be the key player in this process.
- Blachon S, Khire A, and Avidor-Reiss T. The Origin of the Second Centriole of the Zygote. Genetics. Early Online February 13, 2014, doi:10.1534/genetics.113.160523
- Basiri, ML. Blachon S. Chim, YCF, and Avidor-Reiss T. Imaging Centrosomes in Fly Testes. The Journal of Visualized Experiments 2013 Sep 20;(79):e50938. doi: 10.3791/50938
- Avidor-Reiss T. Gopalakrishnan J. Cell Cycle Regulation of the Centrosome and Cilium. Drug Discovery Today: Disease Mechanisms 2013 http://dx.doi.org/10.1016/j.ddmec.2013.03.002
- Gopalakrishnan, J, Chim, YCF, Ha, A, Basiri, ML, Lerit DA, Rusan NM,and Avidor-Reiss, T. Tubulin nucleotide status controls Sas-4-dependent pericentriolar material recruitment. Nature Cell Biol. 2012 Aug;14(8):865-73. doi: 10.1038/ncb2527.
- Gopalakrishnan, J, Blachon S, Bo Z, Smith A, Church A, Nicastro D, Gygi S, and Avidor-Reiss, T. Sas-4 Scaffolds Cytoplasmic PCM Complexes and Tethers them to the Centriole. Nature Communications. 2011 Jun 21;2:359. doi: 10.1038/ncomms1367.
- Gopalakrishnan J, Guichard P, Smith A, Schwarz H, Agard D, Marco S, and Avidor-Reiss T. Self-Assembling SAS-6 Multimer is a Core Centriole Building Block. J Biol Chem. 2010 Mar 19; 285(12):8759-70
- Stephanie Blachon, Xuyu Cai, Kela A Roberts, Kevin Yang, andrey Polyanovsky, Allen
church, and Tomer Avidor-Reiss. A Proximal Centriole-Like Structure is Present in Drosophila Spermatids and can
serve as a model to study centriole duplication. Genetics, 2009 Mar 16. May;182(1):133-44.
This work was cited in Faculty of 1000
- Miller SW, Avidor-Reiss T, Polyanovsky A, Posakony JW. Complex interplay of three transcription factors in controlling the tormogen differentiation program of Drosophila mechanoreceptors. Dev Biol. 2009 Feb 20.
- Blachon S, Gopalakrishnan J, Omori Y, Polyanovsky A, Church A, Nicastro D, Malicki J, Avidor-Reiss T. Drosophila Asterless the Ortholog of Vertebrate Cep152 is Essential for Centriole Duplication. Genetics, 2008 Dec;180(4):2081-94.
- Steiner D, Avidor-Reiss T, Schallmach E, Saya D, Vogel Z. Inhibition and superactivation of the calcium-stimulated isoforms of adenylyl cyclase: role of Gbg dimers. J Mol Neurosci, 2005;27:195-203.
- Steiner D, Avidor-Reiss T, Schallmach E, Butovsky E, Lev N, Vogel Z. Regulation of adenylate cyclase type VIII splice variants by acute and chronic Gi/o-coupled receptor activation. Biochem J, 2005;386:341-8.
- Avidor-Reiss T, Maer AM, Koundakjian E, Polyanovsky A, Keil T, Subramaniam S, Zuker CS. Decoding cilia function: defining specialized genes required for compartmentalized cilia biogenesis. Cell, 2004;117:527-39.
- Nevo I, Avidor-Reiss T, Levy R, Bayewitch M & Vogel Z. Acute and chronic activation of the mu-opioid receptor with the endogenous ligand endomorphin differentially regulates adenylyl cyclase isozymes. Neuropharmacology 2000;39:364-71.
- Rhee MH, Nevo I, Avidor-Reiss T, Levy R, Vogel Z. Differential superactivation of adenylyl cyclase isozymes after chronic activation of the CB(1) cannabinoid receptor. Mol Pharmacol, 2000;57, 746-52.
- Bayewitch ML, Nevo I, Avidor-Reiss T, Levy R, Simonds WF, Vogel Z. Alterations in detergent solubility of heterotrimeric G proteins after chronic activation of G(i/o)-coupled receptors: changes in detergent solubility are in correlation with onset of adenylyl cyclase superactivation. Mol Pharmacol 2000;57:820-5.
- Obadiah J, Avidor-Reiss T, Fishburn CS, Carmon S, Bayewitch M, Vogel Z, Fuchs S & Levavi-Sivan. B Adenylyl cyclase interaction with the D2 dopamine receptor family; differential coupling to Gi, Gz, and Gs. Cell Mol Neurobiol 1999;19:653-64.
- Bayewitch M, Avidor-Reiss T, Levy R, Pfeuffer T, Nevo I, Simonds WF & Vogel Z. Differential modulation of adenylyl cyclases I and II by various Gb subunits. J Biol Chem, 1998;273:2273-6.
- Bayewitch M, Avidor-Reiss T, Levy R, Pfeuffer T, Nevo I, Simonds WF & Vogel Z. Inhibition of adenylyl cyclase isoforms V and VI by various Gbg subunits. FASEB J 1998;12:1019-1025.
- Nevo I, Avidor-Reiss T, Levy R, Bayewitch M, Heldman E & Vogel Z. Regulation of adenylyl cyclase isozymes upon acute and chronic activation of inhibitory receptors. Mol Pharmacol 1998;54:419-26.
- Rhee M-H, Bayewitch M, Avidor-Reiss T, Levy R & Vogel Z. Cannabinoid receptor activation differentially regulates the various adenylyl cyclase isozymes. J Neurochem 1998;71:1525-1534.
- Belcheva M M, Vogel Z, Ignatova E, Avidor-Reiss T, Zippel R, Levi R, Young EC, Barg J and Coscia CJ. Opioid modulation of ERK activity is ras dependent and involves Gbg subunits. J Neurochem 1997;70:635-45.
- Avidor-Reiss T, Nevo I, Saya D, Bayewitch M and Vogel Z. Opioid-induced adenylyl cyclase supersensitization is isozyme-specific. J Biol Chem 1997;272:5040-7.
- Bayewitch M,Rhee MH,Avidor-Reiss T, Breuer A, Mechoulam R and Vogel Z. (-)D9-Tetrahydrocannbinol antagonizes the peripheral cannabinoid receptor-mediated inhibition of adenylate cyclase. J Biol Chem 1996;271:9902-5.
- Avidor-Reiss T, Nevo I, Levy R, Pfeuffer T and Vogel Z. Chronic opioid treatment induces adenylyl cyclase V superactivation: involvement of Gbg. J Biol Chem 1996;271:21309-15.
- Avidor-Reiss T, Zippel R, Levy R, Saya D, Ezra V, Barg J, Matus-Leibovitch N and Vogel Z. k-Opioid receptor-transfected cell lines: modulation of adenylyl cyclase activity following acute and chronic opioid treatments. FEBS Lett 1995;361:70-74.
- Bayewitch M, Avidor-Reiss T, Levy R, Barg J, Mechoulam R and Vogel Z. The peripheral cannabinoid receptor: adenylate cyclase inhibition and G protein coupling. FEBS Lett 1995;375:143-147.
- Avidor-Reiss T, Bayewitch M, Levy R, Matus-Leibovitch N, Nevo I and Vogel Z. Adenylylcyclase supersensitization in µ-opioid receptor-transfected CHO cells following chronic opioid treatment. J Biol Chem 1995;270:29732-8.
- Matus-Leibovitch N, Ezra-Macabee V, Saya D, Attali B, Avidor-Reiss T, Barg J and Vogel Z. Increased expression of synapsin I mRNA in defined areas of the rat central nervous system following chronic morphine treatment. Mol Brain Res 1995;34:221-30.
- Avidor B, Avidor T, Schwartz L, De Jongh KS and Atlas D. Cardiac L-type Ca2+ channel triggers transmitter release in PC12 cells. FEBS Lett 1994;342:209-13.
- Avidor T, Clementi E, Schwartz L and Atlas D. Caffeine-induced transmitter release is mediated via ryanodine-sensitive channel. Neurosci Lett 1994;165:133-6.
28. Avidor-Reiss T. The cellular and developmental program connecting the centrosome and cilium duplication cycle. Semin Cell Dev Biol. 2010 Apr;21(2):139-41.
Avidor-Reiss T. Gopalakrishnan J. Blachon S. Polyanovsky A. Centriole duplication and inheritance in Drosophila melanogaster. The Centrosome: Cell and Molecular Mechanisms of Functions and Dysfunctions in Disease" ed. by Heide Schatten. Edited by Heide Schatten. 2012; Chapter 1: Centriole duplication and inheritance in Drosophila melanogaster. Springer Science and Business Media
Dr. Amitabha Mukhopadhyay
Emily L Fishman