MYH9

The MYH9 protein (myosin heavy chain 9), also known as non-muscle myosin IIA (NMIIA), is an important component of the cellular cytoskeleton. It plays a central role in various cellular processes. Myosins are a large family of motor proteins that share the common features of ATP hydrolysis (ATPase enzyme activity), actin binding and the potential for kinetic energy transfer. Originally isolated from muscle cells, it is known that almost all eukaryotic cells contain myosins.

Main functions of the MYH9 protein:

• Cell shape and movement: MYH9 is involved in the formation and contraction of actin-myosin filaments, which are crucial for the maintenance of cell shape and for cell movement (e.g. migration) (Kunishima S et al. 2010). Plays an important role during cell spreading in cytoskeletal reorganization, formation of focal contacts (at the edges but not in the central part of spreading cells) and lamellipodia retraction; this function is mechanistically antagonized by MYH10 (Betapudi V 2010).
• Cell division (cytokinesis): During cell division, MYH9 contracts the contractile ring structure necessary for the separation of daughter cells.
• Adhesion and cell-cell contacts: The MYH9 protein regulates cell adhesion, i.e. the connection of cells with their environment or with each other - important, for example, for tissue structure and integrity.
• Mechanosensitivity: MYH9 reacts to mechanical forces in the environment and helps the cell to adapt to them (e.g. when the tissue is stretched or compressed).
• Signal transduction: MYH9 is involved in signaling pathways that translate mechanical and chemical stimuli into cellular responses, e.g. during differentiation or stress responses. The RhoA/ROCK and Rac/Cdc42 signaling pathways modulate MYH9 activity in response to cellular stimuli (e.g. stress, migration, differentiation).
• Vesicle transport and endocytosis: It supports the transport of vesicles within the cell, especially through the cytoskeleton.
• Interaction with other proteins: MYH9 interacts with adhesion complexes, integrins, and other cytoskeletal components to coordinate cell structure and movement.
• The MYH9 protein also acts as a receptor for the herpes simplex virus 1/HHV-1 envelope glycoprotein B.

MYH9 (non-muscle myosin IIA) consists of several functional domains:

Head domain (motor domain): Binds ATP and actin; performs ATP hydrolysis, enabling mechanical movement along actin filaments.

Neck region: Binds myosin light chains (MLC), which regulate motor activity.

Tail region: This is responsible for dimerization (binding of two myosin chains) and filament formation. It is used for anchoring to other cell structures or membranes.

The ability to form filaments distinguishes non-muscle myosin IIA from other myosins and is essential for mechanical stability and force transmission in the cell.

Mutations in the MYH9 gene can lead to so-called "MYH9-associated diseases", such as the May-Hegglin anomaly spectrum, which can be associated with thrombocytopenia, kidney problems, hearing loss and cataracts. Malta syndrome (MYH9 associated elastin aggregation) is also caused by a mutation in this gene.

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9. Verver EJ et al. (2016) Nonmuscle Myosin Heavy Chain IIA Mutation Predicts Severity and Progression of Sensorineural Hearing Loss in Patients With MYH9-Related Disease. Ear Hear 37:112-120.