26.11:
Microtubules in Signaling
Microtubules can contribute to cell signaling either as individual filaments or through specialized structures, including primary cilia.
Primary cilia protrude from basal bodies embedded in the plasma membrane. The core of a primary cilium, known as the axoneme, has doublet microtubules arranged in a 9+0 radial arrangement.
Unlike motile cilia, they lack the central pair of microtubules, radial spokes, and axonemal dyneins. These non-motile, hair-like structures act as antennae to interact with the surroundings and relay external signals into the cell.
For example, in the vertebrate retina, a primary cilium is found in rod and cone cells. The outer segment of rod cells has photoreceptors on its surface that receive stimuli and relay them through the primary cilium to the inner segment of rod cells.
The inner segment further transmits the signal through the cell body to a synaptic terminal, where it is released in the form of neurotransmitters, such as glutamate. In synaptic terminals, microtubules help anchor mitochondria and transport synaptic vesicles.
26.11:
Microtubules in Signaling
The primary cilium, made up of microtubules, acts as antennae on the cell surfaces for relaying external stimuli into the cells. These fine hair-like structures are present, generally one per cell. These are non-motile cilia in a 9+0 microtubules arrangement, where the central pair of microtubules are absent. The primary cilia arise from the basal body embedded in the cell membrane. Intraflagellar transport (IFT) carries requisite proteins from the cytoplasm to the cilium because the primary cilium cannot synthesize proteins. These are resistant to microtubule disassembly-causing drugs like colchicine.
The primary cilium plays a role in several key signaling pathways, among which the calcium-dependent signaling pathway has been most widely studied. However, recent studies have highlighted their roles in calcium-independent pathways like Sonic-hedgehog, Wnt, PDGFR, Notch, etc.
In humans, the primary cilium, although found in almost all cell types, but is most common in epithelial cells. They have a key role in the node of the vertebrate, which is responsible for positioning the organs in the developing embryo. The primary cilium moves in a circular motion to create the left-right symmetry for the correct positioning of the visceral organs. A defect in genes responsible for forming primary cilium results in the sinus invertus disorder, where the typical symmetry of the organs in the embryo is lost. Other diseases associated with the defect in primary cilium include Meckel-Guber syndrome, Bardet-Beedle syndrome, polycystic kidney disorder, and Joubert syndrome.
Suggested Reading
- Wheway, G., Nazlamova, L. and Hancock, J.T., 2018. Signaling through the primary cilium. Frontiers in cell and developmental biology, 6, p.8.
- Shinohara, K. and Hamada, H., 2017. Cilia in left-right symmetry breaking. Cold Spring Harbor perspectives in biology, 9(10), p.a028282.