Structural Basis of Cargo Recognition by Unconventional Myosins in Cellular Trafficking

Abstract

Unconventional myosins are a superfamily of actin-based molecular motors playing diverse roles including cellular trafficking, mechanical supports, force sensing and transmission, etc. The variable neck and tail domains of unconventional myosins function to bind to specific cargoes including proteins and lipid vesicles and thus are largely responsible for the diverse cellular functions of myosins in vivo. In addition, the tail regions, together with their cognate cargoes, can regulate activities of the motor heads. This review outlines the advances made in recent years on cargo recognition and cargo binding-induced regulation of the activity of several unconventional myosins including myosin-I, V, VI and X in cellular trafficking. We approach this topic by describing a series of high-resolution structures of the neck and tail domains of these unconventional myosins either alone or in complex with their specific cargoes, and by discussing potential implications of these structural studies on cellular trafficking of these myosin motors.

Unconventional Myosins: How Regulation Meets Function

“…These are further divided into two groups: the group of conventional myosins which include the skeletal, cardiac and smooth muscle myosins and the non-muscle myosin II; and the group of unconventional myosins which represent two-thirds of myosin genes in humans [3]. Unconventional myosins perform key roles in a broad range of fundamental cellular processes, including endocytosis, exocytosis, intracellular trafficking, organelle and plasma membrane morphology, cell adhesions, cell motility and transcription [4][5][6] (Figure 1). Depending on their mechano-enzymatic properties and structural features, they fulfil these roles by acting as cargo transporters, as molecular anchors onto the actin cytoskeleton, as tension sensors, as actin cross-linkers and even as regulators of the actin cytoskeleton itself [5,7].…”

Thermodynamic aspects of ATP hydrolysis of actomyosin complex

“…1) and is driven by hydrolysis of a single ATP molecule bound to myosin. Inside a living cell, the myosin is often physically associated with a cargo, for example, to the thick muscle filament in muscle contraction (Arakelian et al 2015) or to the membrane vesicle in intracellular trafficking (Kruppa et al 2016; Li et al 2016). Multiple myosin proteins may attach to the same cargo simultaneously (Heissler and Sellers 2016a), and they may bind to multiple yet parallel F-actins, pulling the cargo to move along actin filaments.…”

The myosin regulatory light chain Myl5 localizes to mitotic spindle poles and is required for proper cell division

“…Myosins are ATP-dependent actin-based molecular motors that perform a variety of functions in muscle contraction, cargo transport, cell adhesion, and cell division; including spindle assembly, spindle orientation and cytokinesis 16,17 . During cell division, the unconventional myosin-2 (MYO2) is critical for acto-myosin ring contraction during cytokinesis, which is essential for bisecting one cell into two daughter cells 18,19 .…”

“…Therefore, myosins perform important functions that are necessary for a productive cell division. The unconventional myosin holoenzymes typically consists of heavy and light chains 16 . Myosin light chains are required for the structural integrity of the myosin holoenzyme and have regulatory functions on the activity of the protein complex 16,22,23 .…”

“…The unconventional myosin holoenzymes typically consists of heavy and light chains 16 . Myosin light chains are required for the structural integrity of the myosin holoenzyme and have regulatory functions on the activity of the protein complex 16,22,23 . There are two major groups of myosin light chains, the Essential Light Chains (ELCs) and the Regulatory Light Chains (RLCs) 22,23 .…”