Patronin Regulates the Microtubule Network by Protecting Microtubule Minus Ends

Abstract

Tubulin assembles into microtubule polymers that have distinct plus and minus ends. Most microtubule plus ends in living cells are dynamic; the transitions between growth and shrinkage are regulated by assembly-promoting and destabilizing proteins. In contrast, minus ends are generally not dynamic, suggesting their stabilization by some unknown protein. Here, we have identified Patronin (also known as ssp4) as a protein that stabilizes microtubule minus ends in Drosophila S2 cells. In the absence of Patronin, minus ends lose subunits through the actions of the Kinesin-13 microtubule depolymerase, leading to a sparse interphase microtubule array and short, disorganized mitotic spindles. In vitro, the selective binding of purified Patronin to microtubule minus ends is sufficient to protect them against Kinesin-13-induced depolymerization. We propose that Patronin caps and stabilizes microtubule minus ends, an activity that serves a critical role in the organization of the microtubule cytoskeleton.

Nezha/CAMSAP3 and CAMSAP2 cooperate in epithelial-specific organization of noncentrosomal microtubules

“…Nezha [also known as calmodulin-regulated spectrin-associated protein 3 (CAMSAP3)] tethers noncentrosomal microtubules to the adherens junctions via its attachment to the minus ends of these microtubules (8). The Drosophila protein Patronin, which is related to CAMSAP3, stabilizes the minus ends of microtubules by protecting them against Kinesin 13-mediated depolymerization (9). Two other proteins, CAMSAP1 and CAM-SAP2, are also related to CAMSAP3 (10), but their functions remain undetermined.…”

Cytokinesis microtubule organisers at a glance

“…It remains to be determined whether a stabilisation of interpolar microtubules that pre-exist from metaphase is sufficient for the formation of the central spindle or whether de novo microtubule polymerisation (Uehara and Goshima, 2010) is also required. The molecular details of the anchoring of the microtubule minus ends or their stabilisation without a specific anchoring structure are also unclear, although c-tubulin (Julian et al, 1993;Shu et al, 1995) and its associated proteins, such as augmin (Uehara et al, 2009) and minus-end-directed motor kinesin-14 (Cai et al, 2010), as well as the recently identified microtubule minus-end stabiliser patronin (Goodwin and Vale, 2010) have been suggested to be involved. By contrast, the roles of motors and microtubule-associated proteins (MAPs) that localise to the central anti-parallel overlaps have been better characterised as described below.…”

Noncentrosomal microtubules in C. elegans epithelia

“…MT minus-end binding proteins display stabilizing or protecting activities, and largely contribute to noncentrosomal MT generation. C. elegans possesses three known -TIPs (Box 1): g-tubulin and its associated proteins GIP-1 and GIP-2 (Hannak et al, 2002), PTRN-1 [belonging to the conserved Patronin/ Nehza/calmodulin and spectrin-associated family (CAMSAP) (Goodwin and Vale, 2010)], and NOCA-1(noncentrosomal array 1) with homology to ninein (Wang et al, 2015). PTRN-1 function has mostly been described in neurons (Marcette et al, 2014;Richardson et al, 2014), and axon regeneration (Chuang et al, 2014).…”

“…They include the major MT nucleator g-tubulin/TBG-1 and its associated complex containing GIP-1 and GIP-2 (gamma-tubulin interacting protein, formerly called CeGrip-1/2, Hannak et al, 2002); -TIPs also include NOCA-1 (Wang et al, 2015) and the patronin homologue PTRN-1, formerly PQN-34 (Goodwin and Vale, 2010; see main text for details).…”