Linking cortical microtubule attachment and exocytosis

Abstract

Exocytosis is a fundamental cellular process whereby secreted molecules are packaged into vesicles that move along cytoskeletal filaments and fuse with the plasma membrane. To function optimally, cells are strongly dependent on precisely controlled delivery of exocytotic cargo. In mammalian cells, microtubules serve as major tracks for vesicle transport by motor proteins, and thus microtubule organization is important for targeted delivery of secretory carriers. Over the years, multiple microtubule-associated and cortical proteins have been discovered that facilitate the interaction between the microtubule plus ends and the cell cortex. In this review, we focus on mammalian protein complexes that have been shown to participate in both cortical microtubule capture and exocytosis, thereby regulating the spatial organization of secretion. These complexes include microtubule plus-end tracking proteins, scaffolding factors, actin-binding proteins, and components of vesicle docking machinery, which together allow efficient coordination of cargo transport and release.

Keywords: IQGAP1; cargo transport; cytoskeleton; exocytosis; mictrotubules; tracking proteins.

Figure 1.. Schematic overview of IQGAP and associated protein functions in cortical microtubule capturing and exocytosis.

Through its different domains, IQGAP interacts with a subset of microtubule plus-end tracking proteins (+TIPs) (orange) and cortical proteins (blue), thereby facilitating the microtubule capture at sites with high exocytotic activity. At the same time, IQGAP controls multiple components involved in secretion, including exocytotic vesicle-specific Rab GTPases (yellow), the exocyst complex (purple), and actin (red lines). Single-headed arrow, protein interaction with regulatory function; double-headed arrow, protein interaction facilitating recruitment; bar-headed line, negative regulation; dotted arrow, movement in direction of arrow.

Figure 2.. Schematic overview of the cortical microtubule stabilizing complex (CMSC) and associated proteins involved in microtubule capture and exocytosis.

The CMSC (blue) captures microtubules through direct interactions with a specific subset of microtubule plus-end tracking proteins (+TIPs) (orange). CMSC components are found in the proximity of focal adhesions (purple), where they regulate microtubule-mediated focal adhesion turnover. Furthermore, the CMSC has been shown to directly interact with Rab6A/Rab8A-positive vesicles (yellow), thereby facilitating secretion. Double-headed arrow, protein interaction facilitating recruitment; bar-headed line, negative regulation; dotted arrow, movement in direction of arrow.