Kinesin Superfamily Motor Protein KIF17 and mLin-10 in NMDA Receptor-Containing Vesicle Transport

Abstract

Experiments with vesicles containing N-methyl-D-aspartate (NMDA) receptor 2B (NR2B subunit) show that they are transported along microtubules by KIF17, a neuron-specific molecular motor in neuronal dendrites. Selective transport is accomplished by direct interaction of the KIF17 tail with a PDZ domain of mLin-10 (Mint1/X11), which is a constituent of a large protein complex including mLin-2 (CASK), mLin-7 (MALS/Velis), and the NR2B subunit. This interaction, specific for a neurotransmitter receptor critically important for plasticity in the postsynaptic terminal, may be a regulatory point for synaptic plasticity and neuronal morphogenesis.

Neuronal distribution of Spatial in the developing cerebellum and hippocampus and its somatodendritic association with the kinesin motor KIF17

“…6C-D). As previously shown, KIF17 has been detected in abundance in the gray matter, especially in pyramidal cells of the hippocampus [9]. Interestingly, in the hippocampal CA3 region, we observed at high magnification that the characteristic vesicle-like profile staining obtained with the anti-KIF17…”

“…This interaction is restricted to highly organized cytoskeletal structures such as the manchette and the principal piece of the sperm tail. Although the role of KIF17b in these structures is still unknown, the function of the kinesin-2 motor KIF17 in other highly organized cytoskeletal structures, such as the cilia and dendrites, has been well established [7][8][9]. Indeed, KIF17 was shown to transport organelles, vesicles, channels, protein complexes and RNA to specific subcellular compartments in neurons [7][8][9][10].…”

“…Receptors and other proteins synthetized in the cell body are often transported to pre/postsynaptic sites by the kinesin superfamily of proteins (KIFs) [23]. KIF17, a homodimeric microtubule anterograde motor protein, when overexpressed, enhances spatial and working memory in mice [9,24]. Interestingly, Spatial shows the same cellular distribution as…”

Changes in NMDA receptor subunits and interacting PSD proteins in dorsolateral prefrontal and anterior cingulate cortex indicate abnormal regional expression in schizophrenia

“…[24][25][26][27][28][29][30] In addition, binding of newly synthesized NMDA receptor subunits to PSD-95 or SAP102 links the receptor to different intracellular trafficking pathways, which is essential for its trafficking from the ER/Golgi complex to the PSD. [31][32][33][34] Changes in the expression of transcripts encoding NMDA receptor subunits in the prefrontal cortex have previously been described in post-mortem schizophrenic brains. [35][36][37] However, relatively little is known about protein expression of these subunits in schizophrenia.…”

Kinesin motors as molecular machines

“…The adaptor or receptor proteins that couple kinesin motors to proteins associated with membrane-bounded cargo have recently begun to be identified using genetics, yeast two-hybrid screens, and coprecipitation by antibodies. Several of the adaptor or receptor proteins identified so far are components of large complexes that may include other receptor and signaling proteins, e.g., the NR2B subunit of the NMDA neurotransmitter receptor, (14) the AP-1 adaptor complex, (15) amyloid precursor protein (16) and JNK signaling pathway interacting proteins. (17) Transport of specific signaling proteins to particular targets within the cell may be important in regulating their activity.…”