Microtubule-Associated Motor Proteins in Skeletal Development and Health

Extracellular changes resulting in perturbed skeletal development can be a direct result of mutations in the structural extracellular matrix (ECM) components and of changes in the receptor activity and signalling pathways, but also of perturbations to intracellular mechanisms that can have secondary extracellular consequences. The developing cartilage and bone are highly secretory and mechanoresponsive tissues, and the intracellular processes governed by the cytoskeletal proteins and by the associated molecular motors aid in protein processing and secretion, recycling of membrane-bound receptors, positioning of the organelles, maintenance of the primary cilia, modulation of signalling pathways, and coordination of the cell cycle. Molecular motors hydrolyse ATP to generate forces that allow them to travel towards either plus or minus ends of the microtubules generating forces that govern the movement of all intracellular cargo as well as the formation of the mitotic spindle and polar ejection forces during cell division. Their complex structure and diversity allow for varied cargo, from membrane-bound vesicles (lysosomes, endosomes, phagosomes, peroxisomes) to organelles (mitochondria, Golgi apparatus, nucleus), lipid droplets, chromosomes, and nucleic acids (DNA and mRNA). In this chapter, we discuss the microtubule-associated molecular motors, dyneins, and kinesins and their emerging roles in skeletal dysplasia.