Membrane Traffic in the Late Steps of Cytokinesis

Abstract

Cells don't simply separate at cytokinesis. While furrow contraction critically relies on myosin-II and F-actin, post-furrowing steps are less understood but involve the constriction of ESCRT-III polymer-dependent helices on the side of the midbody, which likely drive final abscission. The first evidence that animal cell cytokinesis requires membrane traffic, as in plant cells, was provided about 15 years ago. Since then, it has become increasingly clear that fusion of vesicles to the cytokinetic furrow is essential in large embryonic cells, and that membrane traffic within the intercellular bridge is crucial for its stability and successful abscission in all animal cells. Here, we review our current knowledge of the secretory and endocytic recycling pathways involved in cytokinesis, and how vesicles defined by specific Rab and Arf GTPases are targeted and fused to the membrane of the intercellular bridge thanks to different molecular motors, tethering complexes and SNARE machineries. At the functional level, we will describe how membrane traffic can remodel both phosphoinositide lipids and promote F-actin clearance necessary for ESCRT-III-dependent abscission, and identify key unanswered questions in the field. We will finally review recent evidence showing a tight coupling between membrane traffic and cytokinesis in complex processes, such as during the establishment of de novo apico-basal polarity.

The Flemmingsome reveals an ESCRT-to-membrane coupling via ALIX/syntenin/syndecan-4 required for completion of cytokinesis

“…C ytokinesis leads to the physical separation of daughter cells and concludes cell division. Final abscission occurs close to the midbody (or Flemming body), a prominent structure that matures at the center of the intercellular bridge connecting the two daughter cells and first described by Walther Flemming in 1891 [1][2][3][4][5][6][7][8][9] . The scission occurs not at the midbody itself, but at the abscission site located at distance on one side of the midbody [10][11][12][13][14] .…”

“…Remarkably, ESCRT-III-dependent helices of 17 nm filaments are observed at the abscission site by electron microscopy (EM), and ESCRT-III helical structures are often visible extending from the midbody to the abscission site 10,36 . Therefore, as in other topologically equivalent ESCRT-III-mediated events, including exosome biogenesis in multivesicular bodies (MVBs), retroviral budding or membrane repair, constriction of ESCRT-III filaments likely drives the final membrane scission during cytokinetic abscission [2][3][4][5][6][7]9 .…”

Rab14/MACF2/CAMSAP3 Complex Regulates Endosomal Targeting to the Abscission Site During Cytokinesis

“…Abscission is the last step of mitotic cell division that leads to resolution of the intracellular bridge (ICB) and physical separation of two daughter cells. It is now becoming clear that abscission is a very complex and highly regulated event (Addi et al, 2018;Fremont and Echard 2018;Schiel and Prekeris 2010). Indeed, recent studies identified a new mitotic checkpoint, known as abscission checkpoint (also sometimes referred to as NoCut), that is activated by lagging chromosomes and leads to the arrest of the cells in telophase (Bai et al, 2020;Petsalaki and Zachos 2020;Sadler et al, 2018).…”

“…We now know that abscission involves highly organized remodelling of the cytoskeleton at the ICB. Specifically, the abscission site is defined by localized disassembly of actin cytoskeleton that is presumably a remnant of the cytokinetic contractile ring (Addi et al, 2018;Fremont and Echard 2018;Schiel et al, 2012). Actin depolymerisation then leads to spastin-dependent microtubule severing and formation of ESCRT polymers that eventually drives plasma membrane fusion and resolution of the ICB .…”

“…It is now well-established that endocytic transport plays an important role in regulating abscission; specifically, endocytic Rab11a/b and Rab35 were implicated to mediate this process (Fremont and Echard 2018;Gibieza and Prekeris 2018;. Since numerous Rab GTPases are known to regulate endocytic transport, we set out to identify other endocytic Rab GTPases that may contribute to mediating abscission.…”