Cyclin-dependent Kinase 5 Regulates Cortical Neurotransmission and Neural Circuits Associated with Motor Control in the Secondary Motor Cortex in the Mouse

Ubiquitin ligase activity inhibits Cdk5 to control axon termination

“…Cdk5 is an important regulator of axon and neurite outgrowth [ 48 , 60 – 62 ]. The tyrosine kinases Abl and Fyn positively regulate Cdk5 during neurite outgrowth and growth cone collapse [ 13 , 14 ].…”

Downregulation of CDK5 signaling in the dorsal striatum alters striatal microcircuits implicating the association of pathologies with circadian behavior in mice

“…The sequence used for targeted editing of Cdk5 was 5ʹ-TCAGCTTCTTGTCACTATGC-3ʹ, and the non-specific NC sequence was 5ʹ-CGCTTCCGCGGCCCGTTCAA-3ʹ. Standard procedures and LV/Cas9-sgRNA validation in vivo were reported previously [ 21 ]. Briefly, HEK293T cells were plated in 6-well plates (5 × 10 5 cells/well) and cultured in Dulbecco’s Modified Eagle Medium with 10% fetal bovine serum at 37 °C in 5% CO 2 .…”

“…CDK5 dysfunction is associated with several neurodegenerative disorders, such as AD and PD [ 18 , 19 ]. For example, CDK5 phosphorylates the NMDA receptor subunit NR2B to modulate synaptic transmission [ 20 ] and phosphorylates postsynaptic density protein 95 (PSD-95) to promote synaptic PSD-95 clustering and glutamate transmission [ 21 ]. These findings indicate that aberrant hypoactivation of CDK5 may contribute to neural circuitry disorders in human and rodent brains.…”

Involvement of Cyclin Dependent Kinase 5 in M4 Muscarinic Acetylcholine Receptor-Mediated Cholinergic Transmission within the Mouse Dorsal Striatum

“…), then decapitated and the brains removed. Coronal slices (300 µm thick) containing the striatum (0.2-1.3 mm posterior to bregma) were prepared in ice-cold ACSF (as follows: 124 mM NaCl, 2.8 mM KCl, 1.25 mM NaH 2 PO 4 , 2 mM CaCl 2 , 1.25 mM MgSO 4 , 26 mM NaHCO 3 , 10 mM glucose, pH 7.5, bubbled with 95% O 2 /5% CO 2 ) using a vibrating tissue slicer (MA752, Campden Instruments, USA) as previously described [23]. Slices were submerged for 30 min at 32°C in protective media containing 2.5 mM KCl, 1.…”