Actin and Myosin in Non-Neuronal Exocytosis

Abstract

Cellular secretion depends on exocytosis of secretory vesicles and discharge of vesicle contents. Actin and myosin are essential for pre-fusion and post-fusion stages of exocytosis. Secretory vesicles depend on actin for transport to and attachment at the cell cortex during the pre-fusion phase. Actin coats on fused vesicles contribute to stabilization of large vesicles, active vesicle contraction and/or retrieval of excess membrane during the post-fusion phase. Myosin molecular motors complement the role of actin. Myosin V is required for vesicle trafficking and attachment to cortical actin. Myosin I and II members engage in local remodeling of cortical actin to allow vesicles to get access to the plasma membrane for membrane fusion. Myosins stabilize open fusion pores and contribute to anchoring and contraction of actin coats to facilitate vesicle content release. Actin and myosin function in secretion is regulated by a plethora of interacting regulatory lipids and proteins. Some of these processes have been first described in non-neuronal cells and reflect adaptations to exocytosis of large secretory vesicles and/or secretion of bulky vesicle cargoes. Here we collate the current knowledge and highlight the role of actomyosin during distinct phases of exocytosis in an attempt to identify unifying molecular mechanisms in non-neuronal secretory cells.

Membrane tension spatially organizes lysosomal exocytosis

“…FAs are closely linked to both microtubules (MT) (+) ends (Stehbens and Wittmann, 2012; Stehbens et al, 2014; Seetharaman and Etienne-Manneville, 2019), and the cortical acto-myosin cytoskeleton (Miklavc and Frick, 2020). Surprisingly, MT depolymerization by nocodazole treatment did not reduce clustering (F2D) nor the exocytosis rate (F2E).…”

Dynein acts to cluster glutamate receptors and traffic the PIP5 kinase, Skittles, to regulate postsynaptic membrane organization at the neuromuscular junction

“…The impact of PIP 2 on postsynaptic exocytosis may reflect its role as an important regulator of actin cytoskeleton dynamics. PIP 2 interacts with multiple actin-binding domain proteins and promotes F-actin assembly, potentially driving the extension of the plasma membrane and exocytosis (reviewed in Katan and Cockcroft, 2020; Miklavc and Frick, 2020). Moreover, defects in the spectrin and actin cytoskeletons are common features of mutations exhibiting reduced synaptic terminal growth.…”

Actin Cytoskeletal Dynamics in Single-Cell Wound Repair

“…Microtubule-dependent trafficking facilitated by the motor proteins kinesin and dynein comprises the primary mechanism for long-distance vesicle transport [ 101 , 102 ]; however, microtubule-independent long-distance vesicle transport is possible and can be accomplished through actin nucleation [ 41 ]. Once close to the cell periphery, the cortical actomyosin network plays a central role in mediating vesicle anchoring, docking and fusion with the PM (reviewed in [ 103 , 104 ]); therefore, mesoscopic modulation of the cortical actomyosin network is needed to successfully execute exocytosis. On one hand the network comprises a mechanical barrier preventing vesicle fusion [ 29 ], while on the other hand vesicle fusion cannot occur without some degree of actomyosin-mediated assistance [ 103 , 104 ].…”

“…Once close to the cell periphery, the cortical actomyosin network plays a central role in mediating vesicle anchoring, docking and fusion with the PM (reviewed in [ 103 , 104 ]); therefore, mesoscopic modulation of the cortical actomyosin network is needed to successfully execute exocytosis. On one hand the network comprises a mechanical barrier preventing vesicle fusion [ 29 ], while on the other hand vesicle fusion cannot occur without some degree of actomyosin-mediated assistance [ 103 , 104 ]. Supportive of this biphasic relationship, compound-induced F-actin depolymerization reduced the initial rate of exocytosis in mast cells by impairing actin-mediated vesicle capture and transport, but increased the total level of vesicle secretion by weakening the cortical actin barrier [ 105 ].…”