MAPK8IP3

The protein encoded by this gene shares similarity with the product of Drosophila syd gene, required for the functional interaction of kinesin I with axonal cargo. Studies of the similar gene in mouse suggested that this protein may interact with, and regulate the activity of numerous protein kinases of the JNK signaling pathway, and thus function as a scaffold protein in neuronal cells. The C. elegans counterpart of this gene is found to regulate synaptic vesicle transport possibly by integrating JNK signaling and kinesin-1 transport. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined.

Full Name

mitogen-activated protein kinase 8 interacting protein 3

Function

The JNK-interacting protein (JIP) group of scaffold proteins selectively mediates JNK signaling by aggregating specific components of the MAPK cascade to form a functional JNK signaling module (PubMed:12189133).
May function as a regulator of vesicle transport, through interactions with the JNK-signaling components and motor proteins (By similarity).
Promotes neuronal axon elongation in a kinesin- and JNK-dependent manner. Activates cofilin at axon tips via local activation of JNK, thereby regulating filopodial dynamics and enhancing axon elongation. Its binding to kinesin heavy chains (KHC), promotes kinesin-1 motility along microtubules and is essential for axon elongation and regeneration. Regulates cortical neuronal migration by mediating NTRK2/TRKB anterograde axonal transport during brain development (By similarity).
Acts as an adapter that bridges the interaction between NTRK2/TRKB and KLC1 and drives NTRK2/TRKB axonal but not dendritic anterograde transport, which is essential for subsequent BDNF-triggered signaling and filopodia formation (PubMed:21775604).

Biological Process

Anterograde axonal protein transportISS:UniProtKB
Axon developmentISS:UniProtKB
Axon regenerationISS:UniProtKB
Negative regulation of apoptotic processManual Assertion Based On ExperimentIMP:FlyBase
Positive regulation of JNK cascadeISS:UniProtKB
Protein stabilizationManual Assertion Based On ExperimentIMP:FlyBase
Regulation of JNK cascadeISS:UniProtKB
Vesicle-mediated transportISS:UniProtKB

Cellular Location

Cytoplasm
Golgi apparatus
Cytoplasmic vesicle
Cell projection, growth cone
Cell projection, axon
Cell projection, dendrite
Cytoplasm, perinuclear region
Localized in the soma and growth cones of differentiated neurites and the Golgi and vesicles of the early secretory compartment of epithelial cells. KIF5A/B/C-mediated transportation to axon tips is essential for its function in enhancing neuronal axon elongation.

Involvement in disease

Neurodevelopmental disorder with or without variable brain abnormalities (NEDBA):
A disorder characterized by global developmental delay, impaired intellectual development, delayed walking, poor or absent speech, and variable brain anomalies including perisylvian polymicrogyria, cerebral or cerebellar atrophy, and hypoplasia of the corpus callosum.

PTM

Phosphorylation by ROCK1 is crucial for the recruitment of JNK.