Positioning centrioles and centrosomes

Abstract

Centrosomes are the primary microtubule organizer in eukaryotic cells. In addition to shaping the intracellular microtubule network and the mitotic spindle, centrosomes are responsible for positioning cilia and flagella. To fulfill these diverse functions, centrosomes must be properly located within cells, which requires that they undergo intracellular transport. Importantly, centrosome mispositioning has been linked to ciliopathies, cancer, and infertility. The mechanisms by which centrosomes migrate are diverse and context dependent. In many cells, centrosomes move via indirect motor transport, whereby centrosomal microtubules engage anchored motor proteins that exert forces on those microtubules, resulting in centrosome movement. However, in some cases, centrosomes move via direct motor transport, whereby the centrosome or centriole functions as cargo that directly binds molecular motors which then walk on stationary microtubules. In this review, we summarize the mechanisms of centrosome motility and the consequences of centrosome mispositioning and identify key questions that remain to be addressed.

Figure 1.

Indirect versus direct motor transport. (A) Indirect motor transport occurs when a microtubule (green) nucleated and anchored at the centrosome is engaged by a motor protein, for example, Dynein (purple) at the cell cortex. These motor proteins will exert force on the microtubule thereby moving the centrosome. +/− indicates microtubule polarity. (B) Direct motor transport occurs when motor proteins (orange) anchored to the centriole (blue) engage microtubules (green) and pull the centriole directly along the microtubule as cargo, in this example, Kinesin-1 is moving the centriole toward the microtubule-plus end.

Figure 2.

Centrosome translocation in interphase cells. (A) During cytokinesis of cultured cancer cells, the mother centriole (red) migrates (arrow) into the cytokinetic furrow along the midbody microtubules. Upon abscission, the centriole exits the cytokinetic furrow. (B) Upon interaction between lymphocytes and antigen-presenting cells, centrosomal actin (light blue) disassembles and dynein (purple) clusters at the immune synapse. Microtubule nucleation at the centrosome is increased and these centrosomal microtubules (black) contact the clustered dynein motors, which then pull on the microtubules to move the centrosomes to the center of the immune synapse. +/− indicates microtubule polarity.

Figure 3.

Centrosome transport for ciliogenesis. (A) During cytokinesis in the developing Kupffer’s vesicle, the centrosome (pink) migrates from the basal side of the cell to the cytokinetic furrow in a manner dependent upon the protein Pericentrin (magenta). The centrosomes associate with the midbody (pink) microtubules prior to abscission. After abscission, each centriole will form a single motile cilium. (B) In RPE-1 cells, the centrosome (pink) migrates from the basal to the apical surface to form a primary cilium. Migration occurs via the reorganization of the interphase microtubule array (black) pushing the centrosome through the cytoplasm. (C) In multiciliated cells, centrioles (pink) are amplified and then become enveloped in an actin matrix (light blue). The centrioles then migrate apically where the actin matrix forms the subapical actin network that anchors the centrioles prior to cilia (green) formation. +/− indicates microtubule polarity.

Figure 4.

Direct centriole transport in invertebrates. (A) In the early interphase, Drosophila neuroblasts establish asymmetric pericentriolar material (dark green) distribution around the two centrioles (red and pink). The mother centriole (red) interacts with Kinesin-1 (orange) which then moves it in a plus end–directed manner along the microtubule network. As the cell approaches prophase, the centriole stops moving on the microtubule network and recruits pericentriolar material for bipolar spindle formation (not illustrated here). (B) After an extension of the C. elegans’ sensory neuronal dendrite, one of the two neuron centrioles (pink) migrates along the microtubule network from the cell body to the distal tip of the axon where it forms the sensory cilium (green). The centriole migrates via an interaction with the minus end–directed microtubule motor Dynein (purple). +/− indicates microtubule polarity.

Figure 5.

Centrosome positioning in gametogenesis. (A) During spermiogenesis, the centrosome (pink) acts as a linker between the nucleus (head) and axoneme (tail). To facilitate this interaction, dynein (purple) accumulates on one side of the nuclear membrane. Dynein then pulls on centrosomal microtubules to position the centrosome adjacent to the nucleus where it then builds the sperm axoneme (green). (B) Oogenesis occurs in a cyst of interconnected cells. To ensure only one MTOC is present in the oocyte (yellow), centrosomes (pink) migrate through the nurse cells (nude) along the fusome (blue). +/− indicates microtubule polarity.