On May 30th, PNAS published a report from ION entitled “Microtubule affinity-regulating kinase 2 functions downstream of the PAR-3/PAR-6/atypical PKC complex in regulating hippocampal neuronal polarity”. This work was done by Dr. Yan-min Chen and his fellow graduate students from the Laboratory of Synaptic Signaling, under the supervision of Dr. Zhen-ge Luo.

Neurons receive information through their dendrites and send signals to other neurons via their axons. Thus, the proper polarization of neurons is important for the formation of neural circuits. However, the molecular mechanisms underlying neuronal polarization is not well defined. Recently the Laboratory of Synaptic Signaling, headed by Dr. Zhenge Luo, demonstrated a novel mechanism underlying axonal-dendritic polarization. They report a role for PAR-1/MARK, a microtubule affinity-regulating kinase, in axonal-dendritic specification. Knocking down MARK2 expression with small interfering RNAs induced formation of multiple axon-like neurites and promoted axonal outgrowth. Ectopic expression of MARK2 caused phosphorylation of tau (S262) and led to loss of axons, a phenotype rescued by expression of PAR-3, PAR-6, and aPKC. The authors propose that aPKC in complex with PAR-3/PAR-6 negatively regulates MARK(s), which in turn causes dephosphorylation of MAPs, such as tau, leading to the assembly of microtubules and elongation of axons. In short, this study revealed a novel mechanism underlying axon formation and could contribute towards our understanding of nerve injury and neurodegeneration. This work was supported by grants from the Chinese Academy of Sciences, the National Natural Science Foundation of China, and the Shanghai Science and Technology Development Foundation.