A centrosomal scaffold shows some self-control

Abstract

The scaffolding protein AKAP350A is known to localize to the centrosome and the Golgi, but the molecular details of its function at the centrosome remain elusive. Using structure-function analyses, protein interaction assays, and super-resolution microscopy, Kolobova et al. now identify AKAP350A's specific location and protein partners at the centrosome. The authors further define an autoregulatory mechanism that likely controls AKAP350A's ability to nucleate microtubule growth.

Figure 1.

AKAP350 is controlled by an autoregulatory mechanism. A, the distinct localizations of AKAP350 and pericentrin (both of which contain PACT domains (black dots) at the centrosome. Specifically, AKAP350 (blue) localizes to the intercentriole linkage (orange), while pericentrin (pink) localizes to the proximal end of centrioles (olive). Cdk5RAP2 (green) is anchored to the centrosome by pericentrin; it remains unknown if AKAP350 also positions Cdk5RAP2 at the centrosome. B, a rough sequence map captures AKAP350A's autoregulatory mechanism as identified by Kolobova et al. (4). The gray-shaded area, which was the focus of the authors' work, contains the newly discovered inhibitory domain (Inh, red), which regulates the ability of the newly discovered promoting domain (green) to interact with Cep68, Cep170, and Cdk2RAP5. The inhibitory domain may be sensitive to cell state based on overlap with a previously identified site that interacts with RIIα (see text for details (9)). The precise role of AKAP350 at the intercentriole linker (Q1) and the centrosome (Q2) remains unclear.