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Lessons from Bacterial Homolog of Tubulin, Ftsz for Microtubule Dynamics

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Lessons from Bacterial Homolog of Tubulin, Ftsz for Microtubule Dynamics 249 R R Battaje and D Panda Assembly dynamics of FtsZ and 24:9 T1–T21 Thematic Review microtubules Lessons from bacterial homolog of tubulin, FtsZ for microtubule dynamics Correspondence Rachana Rao Battaje and Dulal Panda should be addressed to D Panda Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai, India Email [email protected] Abstract FtsZ, a homolog of tubulin, is found in almost all bacteria and archaea where it has a Key Words primary role in cytokinesis. Evidence for structural homology between FtsZ and tubulin f FtsZ assembly came from their crystal structures and identification of the GTP box. Tubulin and FtsZ f microtubules constitute a distinct family of GTPases and show striking similarities in many of their f cell division polymerization properties. The differences between them, more so, the complexities f anticancer drugs of microtubule dynamic behavior in comparison to that of FtsZ, indicate that the f antibacterial drugs evolution to tubulin is attributable to the incorporation of the complex functionalities in higher organisms. FtsZ and microtubules function as polymers in cell division but their roles differ in the division process. The structural and partial functional homology has made the study of their dynamic properties more interesting. In this review, we focus on the application of the information derived from studies on FtsZ dynamics to study Endocrine-Related Cancer Endocrine-Related microtubule dynamics and vice versa. The structural and functional aspects that led to the establishment of the homology between the two proteins are explained to emphasize the network of FtsZ and microtubule studies and how they are connected. Endocrine-Related Cancer (2017) 24, T1–T21 Introduction Microtubules are major cytoskeletal protein structures of progress in understanding the mechanism of assembly the eukaryotic system involved in cell division forming and the various associating factors that play important the primary components of the mitotic apparatus. roles in it. Microtubules also form flagellar and ciliary structures Microtubules play a significant role in metaphase for cell transport, maintain the cell polarity and are and anaphase of mitosis. They are the key components involved in cell signaling (Nogales 2001). Defective of the mitotic spindle apparatus, which is responsible for microtubules would lead to abnormal morphology of the the segregation of chromosomes (Kline-Smith & Walczak cell and ultimately cell death if the division machinery 2004, Kwon & Scholey 2004). During the metaphase, is impaired. Microtubules are made up of protofilaments the plus ends of microtubules undergo elongation and of tubulin subunits, which assemble to form the highly shortening for probing and binding to the kinetochores. dynamic structures. Microtubule assembly is a highly This is called ‘search and capture’ function (Rieder et al. complex process that has been studied for the past five 1986). The chromosomes are then translocated to the decades and yet, so many mysteries are to be unraveled. equatorial plane, during which, the highly dynamic However, numerous studies have made significant microtubules are stabilized to separate the chromosomes http://erc.endocrinology-journals.org © 2017 Society for Endocrinology This paper forms part of a special section on 50 Years of Tubulin. The Guest Editors DOI: 10.1530/ERC-17-0118 Printed in Great Britain for this section were Karen Crasta and Ritu Aneja. Published by Bioscientifica Ltd. Downloaded from Bioscientifica.com at 09/27/2021 12:57:41PM via free access 10.1530/ERC-17-0118 Thematic Review R R Battaje and D Panda Assembly dynamics of FtsZ and 24:9 T2 microtubules in the following anaphase (Higuchi & Uhlmann 2005). common ancestor. Structural aspects have been covered Chromosomes get pulled toward the poles due to the in the first section. The dynamics of the two proteins shortening of microtubules (Rieder et al. 1994). This entire have been compared in the following section. In the process is dependent on the dynamicity of microtubules next section, some proteins belonging to FtsZ/tubulin and an obstruction would lead to the arrest of the cell superfamily, which act as connecting links between division at the spindle checkpoint (Logarinho et al. 2004). the two proteins have been mentioned. A section on Thus, agents that target the microtubules and hamper their microtubule-targeting agents and FtsZ-targeting agents dynamics can be potential anticancer, anti-fungal and and a comparison of their binding sites has been included anti-parasitic drugs (Jordan & Wilson 2004, Singh et al. to emphasize the significance of such interrelated studies 2008b). The use of anti-microtubule agents as anticancer between FtsZ and microtubules. drugs has been studied extensively (Jordan & Wilson 2004). In addition, it has been indicated that cell stress Discovery of FtsZ and establishing homology response is mediated by microtubules and their interacting with tubulin partners (Parker et al. 2014). In several types of tumors, alterations in the expression of tubulin isotypes and Several genes in the fts regions of the E. coli chromosome microtubule-associated proteins and post-translational were identified while studying the effects of DNA damage modifications have been observed (Parker et al. 2014). on cell such as the elongation of cells and the inhibition The understanding of signaling pathways and response of division (Van de Putte et al. 1964). These genes were mechanisms with respect to microtubules will help in involved in causing filamentous growth, a property that designing new chemotherapeutic drugs. was temperature sensitive (Van de Putte et al. 1964). One of Microtubule dynamics has been a subject of the genes in the 2-min region of E. coli genome disrupted extensive research since the discovery of tubulin, yet, the septum formation when mutated (Hirota et al. 1968). the mechanism is not fully understood. Complications This gene was later given the name ftsZ to separate it from in studying microtubules arise from the inability to the other fts genes of the region (Lutkenhaus et al. 1980). It express the protein in bacterial expression systems. Post- was found to be the target of cell division inhibitor during translational modifications of tubulin are not possible SOS response in E. coli, which shed light on its central inside bacterial cells due to the lack of chaperones and role in the cell (Hirota et al. 1968, Lutkenhaus & Donachie protein co-factors. Thus, the extraction and isolation of 1979, Lutkenhaus et al. 1980, Lutkenhaus 1983). Endocrine-Related Cancer Endocrine-Related tubulin from eukaryotic cells like yeast is the preferred FtsZ was first characterized as a cytoskeletal protein method of purifying the protein. This triggered the search based on experiments that determined the location of for the homolog of tubulin in prokaryotes. the protein. It has been found to be uniformly distributed Many bacterial species such as cyanobacteria, throughout the cell during the growth phase and to form azotobacteria, mycoplasmas, enteric bacteria and a ring-like structure at the mid-position in the dividing archaebacteria were found to contain cytoplasmic tubules, cells (Bi & Lutkenhaus 1991). An overproduction of FtsZ but whether or not these were related to microtubules in cells using multicopy plasmids induced the formation and tubulin was a question of interest (Bermudes et al. of additional septa (other than the medial septa for cell 1994). About 20 years after the discovery of tubulin, FtsZ, division), which resulted in the production of minicells initially thought to be the homolog of actin, arose as the (Ward & Lutkenhaus 1985). The ring structure formed by candidate for being the tubulin homolog in prokaryotes FtsZ was proposed to be involved in constricting the cell (Erickson 1995). FtsZ is the first of several proteins that gets wall to form the septum (Erickson 1995). Even though assembled at the division site in prokaryotes, to form the the function of FtsZ was similar to actin (which forms Z-ring, which is in association with other proteins forms the contractile ring and cleavage furrow in eukaryotes), the divisome (Margolin 2005). Over the years, numerous the two proteins were not found to be homologous (Bi & studies have been done on this bacterial cell division Lutkenhaus 1991). protein and several reports indicated striking similarities A 7-amino acid segment conserved in FtsZ called as well as differences between FtsZ and tubulin. the G-box motif (SAG)GGTG(SAT)G was also found Since the discovery of FtsZ, studies on FtsZ dynamics to be conserved across tubulin from different species have influenced the study of microtubule dynamics and (Mukherjee et al. 1993). Another segment (KR)GXXXXG vice versa. In this review, we focus on the similarities and is present at the inverted P-loop region of the two differences between the two proteins, believed to have a structures (Hesse et al. 1987, Sternlicht et al. 1987, http://erc.endocrinology-journals.org © 2017 Society for Endocrinology Published by Bioscientifica Ltd. DOI: 10.1530/ERC-17-0118 Printed in Great Britain Downloaded from Bioscientifica.com at 09/27/2021 12:57:41PM via free access Thematic Review R R Battaje and D Panda Assembly dynamics of FtsZ and 24:9 T3 microtubules Mukherjee et al. 1993, De Pereda et al. 1996). These Confirming the homology of FtsZ and are related to the GTPase family sequence motif tubulin through X-ray crystal structures GXXXXGK(ST) (Bourne et al. 1991). The probable Microtubules are polymers of tubulin heterodimers. They homology of FtsZ to tubulin triggered a series of are composed of two classes of tubulin- and (Bryan & experiments to test whether FtsZ showed similar α β Wilson 1971, Amos & Klug 1974). Many additional biochemical properties as that of tubulin. FtsZ binds to classes of tubulin have been identified to date. tubulin GTP and hydrolyzes it to GDP, a property also observed γ is involved in the nucleation of the microtubules and with tubulin (de Boer et al.
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