S6K and PDK1 modulate neuronal size specification

Synapse is located in the nervous system and a structure that passes an electrical or chemical signalfrom a neuron to another cell. The presynaptic terminal is a specialized area within the axon of the presynaptic cell that contains neurotransmitters enclosed in small membrane-bound spheres called synaptic vesicles. Active zones is a region that synaptic vesicles are docked at the presynaptic plasma membrane.

Axon diameter, dendrite diameter, the size of a dendritic field, and the area of the presynaptic nerve terminal are reported to be specified for each neuron type, and neuronal size and shape are essential to the generation of neural circuitry. Some studies reported that control of neuronal dimension may be the genes related to the regulation of cell size, including mammalian target of rapamycin, PDK1, and S6 kinase(S6K).

In the paper published September 19, 2011, Cheng et al. took advantage of S6Kl-1 mutation Drosophila to explore the role of S6K and PDK1 in the control of neuronal size. First, S6K localizes to the presynaptic active zone via a Brp-dependent mechanism and its kinase activity is shown to regulate presynaptic bouton size and active zone number without altering bouton number. These data indicate that S6K is necessary for normal synaptic function.PDK1 is essential for activating several kinases, including S6K. Study found that PDK1 is located in neuromuscular junction and also regulates bouton size and active zone number, Further study suggests that PDK1 regulates bouton size through activation of S6K, while PDK1 can also influence total bouton number through another pathway, independent of S6K[1].

In conclusion, S6K and PDK1 have a functional relationship and modulate neuronal size specification.

Reference
[1]. J. Cell Biol. Vol.2011 194 No.; 6;921–935

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S1556	PHT-427	PHT-427 (CS-0223) is a dual Akt and PDPK1 inhibitor (high affinity binding for the PH domains of Akt and PDPK1) with Ki of 2.7 μM and 5.2 μM, respectively.

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S6 Kinase