Biology oj the Cell 91 (1999) 367-378 o 1999 Editions scientifiques et mtidicales Elsevier SAS. All rights reserved

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Review

Polarities of the centriolar structure: Morphogenetic consequences Janine Beisson a and Maria Jerka-Dziadosz a,b aCentre de Gr%&ique MolkAaire du CARS, allbe de la Terrasse, 91198 Gif-sur-Yvette, France; bM.Nencki Institute of Experimental Biology, Polish Academy of Science, Pasteura 3, 02-093 Warsaw, Poland

Centrioles and basal bodies are two versions of the same conserved eukaryotic organelle and share two remarkable properties: nine-fold symmetry of their microtubular shaft and capacity to generate a new organelle in a fixed geometrical relationship to the mother organelle. It can thus be postulated that what is true for basal bodies is likely to be true also for centrioles. While the functions of centrioles are difficult to dissect, the functions of basal bodies are easier to approach. Over more than two decades, studies on protists have led to the notion that ciliary and flagellar basal bodies display polarities, not only a proximo-distal polarity, like in centrioles, but also a circumferential polarity accorded to the polarities of the cell and of its cytoskeleton. The major cytological and genetical data, mainly on Chlamydomonas, Paramecium and Tetruhymenu, which support the notion that the microtubule triplets of basal bodies are non-equivalent, are reviewed. The morphogenetic implications of this circumferential anisotropy, perpetuated through the process of basal body duplication itself, are discussed. The question is raised of the possibility that centrioles also display a circumferential polarity, like basal bodies, and whether at least certain of their functions depend on such asymmetries. 0 1999 I?ditions scientifiques et mbdicales Elsevier SAS

centriole / basal body / cellular polarity / morphogeneis / cytotaxis

THE CENTRIOLAR STRUCTURE The centrioles, which form the core of the centrosome of animal cells, and the basal bodies present at the base of cilia and flagella are two functionally distinct versions of the same totally conserved eukaryotic organelle: a short cylinder ca 250 nm in diameter, composed of triplets of microtubules arranged in a nine-fold radial symmetry, with some variability in the length and ultrastructural details, depending on the organisms or cell types. The remarkable geometric design of this centriolar structure has prompted imaginative hypotheses concerning its origin and functions (Margulis, 1978; Bornens, 1978; Albrecht -Buehler, 1981). The functions of centrioles, despite their ubiquity, remain elusive, partly because they are not easily dissociated from the function of the centrosome itself as a microtubule organizing center. If the function depends on the structure, as it seems reasonable to

assume, then part or all of the function(s) of centrioles should be shared by the kin organelle, the basal body. Indeed, basal bodies and centrioles have in common their two most striking features: nine-fold symmetry of their microtubular shaft and capacity to generate a new organelle in a fixed geometrical relationship to the mother organelle. Furthermore, basal bodies and centrioles are, in diverse physiological situations, interconvertible: centrioles become basal bodies in primary cilia or in spermatozoa or they generate basal bodies in ciliated epithelial cells. Conversely, in many protists, flagellar basal bodies act as centrosomes to organize the mitotic spindle. Finally, the tubular shaft of both

basal bodies and centrioles displays a similar structural and functional polarity along its longitudinal axis. Serial sections of centrioles reveal a ‘graduated proximo-distal architecture’ (Paintrand et al, 1992); satellites or appendages mark the distal part (Rieder and Borisy, 1982; Baron and Salisbury, 1988;

Polarities of the centriolar structure: Morphogenetic consequences

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Biology ot the Ceil 91 (1999) 367-318

Paintrand rt al, 1992; Lange and Gull, 1996) at least of the mother centriole. while more proximal appendages are generally present on basal bodies. The proximal end displays a cartwheel and, in both centrioles and basal bodies, it is the end close to which the procentriole or new basal body arises. The ‘distal’ end is the site from which ‘1 cilium or flagellum can develop. Beyond these simi.larities, basal bodies in protists exhibit a circumferential polarity or anisotropy which, if present, cannot be directly observed in animal cell centrioles. Indeed, in protists, basal bodies and their appendages are constrained within the cytoskeletal framework which provides landmarks to ascertain their localizations and polarities. Each type of appendage develops with a defined orientation and from a particular sector of the basal body cylinder. It thus seems that triplets differ in their capacity to gener--ate appendages, and that basal bodies have anter cif). What i> remarkable is that basal feet develop before the basal bodies reach their membranar site and beL)rc* they acquire their functional orientation (BoisvieuxUlrich crf nl, 1985). The phenomenon is identical to the previl,usiy mentioned development of the cili ate oral apparatus nihere newlv formed basal hodies, with their appendages and even cilium, art) randomly oriented before they become stabilized in =r uniform functional orientation. Other indications of the non-equivalence of triplets can be inferred from morphological specializations among doublets sim-, ilar to those previously noted by Hoops and Wit-man (1983) in Cl~ln~~~l/li~nlo,nm~: for example, in sperm flagella of fish, particular doublets present an internal differentiation, as a partition inside the A tubule yielding different species-specific pattern,< (Mattei, 1988). Except in the process of ciliation, centrioles fun:tion as a pair, the asymmetry of which is attested by cytological, biochemical and physiological data Cytologically, structural differences persist throughout the cell cycle (Vorobjev and Ch.entso\ 1982; Paintrand P/ rzl, 1992; Chretien tlf 1~1,1997) with satellites present only on the mother organelle. Bio-

Polaritiesof the centriolar structure: Morphogenetic consequences

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Biology of the Cell 91 (1999) 367-378

chemically, old and new centrioles may differ by the presence of specific proteins, like cenexin (Lange and Gull, 1995). Physiologically, the primary cilium which develops in many tissues is generated by the old centriole (Lange and Gull, 1996). Most importantly, mother and daughter centrioles display a unique spatial relationship: not only is their configuration orthogonal, but the axis of the daughter centriole intersects the parent and not the reverse, as described by Reider and Borisy (1982). If the orthogonal configuration is not always verified (depending on the physiological conditions or the cell types), nevertheless the rule strictly applies to newly formed centrioles. This indicates that the site of formation of a new centriole is precisely determined and it is tempting to suggest that, as in the case of basal bodies, the new centriole develops in relation to a specific quadrant of the mother centriole. It thus seems that in pro&s and in metazoa, the triplets of basal bodies are non-equivalent and this property is likely to be propagated through the duplication process, most likely by the process itself, especially if duplication is templated by a disc from the cartwheel as proposed by Mignot (1996b) and also considered by Krioutchkova and Onishchenko (1999).

CENTRIOLES AND TRANSMISSIONRECEPTION OF SPATIAL CUES From experiments on various cellular systems, it appears that the centrosome does nol direct a cell’s migration on a substrate and their variable localization in different cell types rather seems to follow the reorganization of the cytoskeleton upon stimulation and movement (Rogers et al, 1985; Gudima et al, 1988; Buendia et al, 1990; Schiitze et al, 1991). However, these observations on the location of the centrosome within the cell tell nothing of the orientation of the centrioles themselves with respect to the cell movement. This orientation may not be random: in migrating 3T3 cells, the primary cilium lies parallel to the substrate and the axis of the companion centriole perpendicular to the substrate (Albrecht-Buehler and B&hnell, 1979); in PE cells, the mother centriole is perpendicular to the spindle axis (Vorobjev and Chentsov, 1982). Even if this orientation results from constraints exerted by the microtubule cytoskeleton emanating from the centrosomes, it nevertheless suggests that the orientation of the axis of the mother centriole might be related to the asymmetry of the cytoskeleton. In particular, the circumferential polarity of the centriole might be responsible for the spindle/aster duality, that is the generation in opposite directions of microtubule arrays with different properties and functions. This duality appears crucial in division

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and development. Indeed, while it seems well established that centrioles are not required for spindle assembly (Waters and Salmon, 1997; Compton, 1998; Hyman and Karsenti, 1998, for reviews), no astral structure develops in the absence of centrioles: this fact distinguishes between a centrosome and a non-centrosomal MTOC, and might help sort out the true contribution of centrioles. Anastral mitoses naturally exist as in the early stages of mouse development (Schatten et al, 1985) or can be obtained by experimental or genetical manipulations. Various mutations affecting the aster in Dvosophila (Craig and Brink, 1996; Wilson et al, 1997; Bonaccorsi ef al, 1998)‘ parthenogenetic activation of Sciara embryos devoid of centrioles (de Saint Phalle and Sullivan, 1998) lead to abnormal development or morphogenesis primarily due to defective nuclear positioning and defective interaction of the aster with the cortex. The implication of astral microtubules in normal development is well documented, especially for asymmetric cell divisions as for example in the nematode in controlling cleavage spindle orientation, by interaction between the aster and cortical sites (White and Strome, 1996), in the mussel Dreissena polymorpha where the spiral segmentation depends on aster asymmetry (Luetjens and Dorresteijn, 1998) or the early Tubifex embryo where asymmetry results from an asymmetric spindle, with a single centrosome and a single aster (Schimizu et al, 1998). In these situations, the precise orientation of the centrioles and the resulting bipolarity of the spindle poles may be an important parameter to interpret and transmit spatial cues related to cell or embryo polarities by interactions between cortical anchors and aster microtubules. Raff and Glover (1989) showed that, in Drosophila, the movements of nuclei to the embryo cortex are mediated by forces acting on the centrosomes rather than on the nucleus itself. Asters are presumably the main target of such forces. It is then conceivable that the microtubules nucleated on either side of the centrosome and which display different characteristics are nucleated under the influence of opposite sides of the centriolar shaft, just as different appendages arise from basal bodies. The situation in S ceveuisiae gives some support to the idea: the spindle pole body, functional equivalent of the centrosome, displays a marked structural and functional bipolarity with an intranuclear spindle and an aster of cytoplasmic microtubules. Like in metazoa, defective astral microtubules lead to defective nuclear positioning and defective budding (Huffaker et al, 1988; Palmer et al, 1992; So&s and Adams, 1998). The biochemical and physiological differences between the two microtubule arrays are already well documented. Different gamma-tubulin

Polaritiesof the centriolar structure: Morphogenetic consequences

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binding complexes interacting with the inner or outer plate respectively, are involved in the nucleation of the two microtubule arrays (SOUPS and Adams, 1998; Knop and Schiebel,l998; Elliot et aI, 1999). A given mutation in the single p-tubulin gene affects differentially spindle and cytoplasmic microtubules (Reijo et al, 1994). In the fungus N haemafococca, aster formation requires a dynein (Inoue et al, 1998). Similar differences between spindle and aster exist in metazoa: it remains to be demonstrated that they reflect centriole asymmetry. As Bovery’s hypotheses are being resurrected (Brinkley and Goepfert, 1998; Doxsey, 1998) with still more emphasis on centrosome than on centrioles, it seemstimely to reconsider the role of centriole in the maintenance of cell polarity and to stress the fact that centrioles, by their structure and mode of templated and polarized duplication, can be a source or a relay in the establishment and maintenance of polarities not only in protists but also in metazoa.

AC

EDGMEhITS

We are much indebted to Linda Sperling, Michel Wright and Jean-Pierre Mignot for critical reading of the manuscript and helpful suggestions.

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