CLASPs at a glance

Abstract

CLIP-associating proteins (CLASPs) form an evolutionarily conserved family of regulatory factors that control microtubule dynamics and the organization of microtubule networks. The importance of CLASP activity has been appreciated for some time, but until recently our understanding of the underlying molecular mechanisms remained basic. Over the past few years, studies of, for example, migrating cells, neuronal development, and microtubule reorganization in plants, along with in vitro reconstitutions, have provided new insights into the cellular roles and molecular basis of CLASP activity. In this Cell Science at a Glance article and the accompanying poster, we will summarize some of these recent advances, emphasizing how they impact our current understanding of CLASP-mediated microtubule regulation.

CLASP2 stabilizes GDP-associated terminal tubulins to prevent microtubule catastrophe

“…Because the amino acid composition of the GTP-binding pockets in different proteins is diverse, these alignments do not rule out that human CLASP2α can be regulated directly by GTP. Interestingly, the conserved NKxD motif localizes to the TOG2 domain, which is responsible for the microtubule-stabilizing activity of CLASP2 ( 6 ). We therefore hypothesized that 1) the TOG2 domain is involved in GTP-dependent microtubule-end binding, and 2) this regulation requires the NKFD sequence.…”

“…By leveraging DNA origami technology and bead-tethering assays, we investigated the molecular activities of CLASP2α amplified by their clustering and without the interference from EB proteins, which are themselves potent regulators of microtubule structure and dynamics (55). Integrating these results with prior work by others (reviewed in (6,56)) leads to a specific model for CLASP2-dependent stabilization of microtubule dynamics.…”

“…CLASPs are an evolutionarily conserved family of ubiquitous factors that exert stabilizing effects on microtubules by suppressing catastrophes and promoting rescues ( 1–4 ). CLASPs importance has been recognized and extensively characterized in a variety of cellular and organismal systems, such as during cell migration, neuronal development, cytoskeleton reorganization in interphase and during cell division (reviewed in ( 5, 6 )). CLASPs are highly potent regulators of the growing microtubule plus-ends, owing to their enrichment at these sites via the tip-binding proteins, such as EB.…”

Several Fusion Genes Identified in a Spermatic Cord Leiomyoma With Rearrangements of Chromosome Arms 3p and 21q

“…Microtubules switch between phases of growth and shrinkage through transitions known as microtubule catastrophe and rescue (84) microtubule growth or shrinkage (85,86). CLASP2 functions in various microtubule-dependent processes including cell division, cytoskeletal remodeling for cell migration, and vesicle transport between intracellular structures and the plasma membrane (87). CLASP2 protein has multiple HEAT repeats, a structural motif composed of two alpha helices linked by a short loop (88), two domains from tumour overexpressed gene that interact with αβ-tubulin, contributing to microtubule dynamics (89,90), a region for interaction of microtubule-associated protein RP/EB family member 1 (MAPRE1, also known as EB1) (85,91), and a carboxyl terminal region which interacts with CLIP1 protein and is required for the localization of CLASP2 protein to the Golgi apparatus and kinetochores (92).…”

Phospho‐regulation of mitotic spindle assembly

“…Once activated, Aurora A phosphorylates TPX2 at Ser121 and Ser125, promoting an interaction between TPX2 and CLASP1, a microtubule stabilizing protein (Lawrence, Zanic, & Rice, 2020), and consequently normal spindle length (Fu et al, 2015). Similarly, Aurora…”