A new role for Rab GTPases during early mitotic stages

Abstract

A recent study revealed new roles for the Rab11 GTPase during mitosis. Rab11 is involved in recycling endosome localization to mitotic spindle poles via dynein-mediated transport. This process is in contrast to Golgi membranes, which disperse in mitosis and do not appear to directly contribute to mitotic functions. Rab11-depletion prevents recycling endosome organization at spindle poles, delays mitotic progression, and disrupts spindle pole protein recruitment, astral microtubule organization, and mitotic spindle orientation. However, Rab11 is not the only endocytic and/or trafficking protein that regulates mitotic progression. Clathrin and two small GTPases (Rab6A', Rab5) play key roles in spindle organization and function. In this commentary, we discuss the roles of all these canonical endocytic and membrane trafficking proteins during mitosis and speculate on possible crosscommunication between them and their molecular pathways that ensure faithful progression through mitosis. IntroductionIt has been known for some time that the recycling endosome is organized around the "centrosome region" 1 . However, a direct relationship between these intracellular elements remained unclear until 2012 when electron microscopy revealed an intimate interaction with a substructure of the centrosome, the mother centriole appendages.2 Mother centriole appendages have become a focus of interest because they functionally define the "older" centriole of the centriole pair. This has important consequences in biology. For example, the older centriole remains in the stem cell, where Rab11-membranes accumulate, while the cell with the younger centrosome undergoes differentiation. 3,4 The mother centriole also templates cilia formation 5 and regulates membrane recycling through Rab11. 2The role of the mother centriole was further identified to modulate Rab11-activity through organization of recycling endosome machinery.2 If appendages were disrupted, recycling endosome machinery (e.g., the exocyst and the Rab11 GTPase Activating Protein, EVI5) were dispersed.2 However, what this study did not demonstrate was whether recycling endosomes contributed to the organization and function of the centrosome. A follow-up study went on to show that the recycling endosome contributes to the organization of the mitotic spindle poles and organization of the spindle. A Novel Role for Rab11-Endosomes in Spindle Pole MaturationEarlier work in Caenorhabditis elegans identified a role for Rab11-endosomes during mitosis. 6,7 These studies showed that depletion of Rab11 caused spindle misalignment through disruption of astral microtubule arrays.

Methods to analyze novel liaisons between endosomes and centrosomes

“…More specifically, we identified a direct interaction between endosomes (loaded with a marker) and appendages of the older/mother centriole of the centriole pair (Hehnly, Chen, Powers, Liu, & Doxsey, 2012). At the RE, two Rab GTPases, Rab8 and Rab11, regulate cargo recycling into and out of the organelle (Das et al, 2014;Grosshans, Ortiz, & Novick, 2006). More recently, studies showed that these GTPases and other RE components interact directly with mother/older centriole appendage proteins.…”

“…centrosome, is poorly understood (Das, Hehnly, & Doxsey, 2014). During interphase, extracellular material at the plasma membrane is endocytosed, passed through the early endosome to the RE (Figure 1).…”

Endosomal Wnt signaling proteins control microtubule nucleation in dendrites

“…Indeed, the localization of Axin to centrosomes [54,55] suggests that even in mitotic cells, parts of this relationship are conserved. Intriguingly, endosomal membranes are concentrated around the centrosome [86], and Rab5 reduction disrupts mitosis [86][87][88], so it is possible that Wnt signaling proteins, endosomes, and nucleation function together at centrosomes.…”

New frontiers: discovering cilia‐independent functions of cilia proteins

“…The same GTPases that function in ciliogenesis are also bona fide endosome components that play important roles in endosome recycling . The centrosome has recently been shown to be involved in organizing and mediating the recycling branch of endosomal trafficking .…”