Specific depletion of the motor protein KIF5B leads to deficits in dendritic transport, synaptic plasticity and memory

Abstract

The kinesin I family of motor proteins are crucial for axonal transport, but their roles in dendritic transport and postsynaptic function are not well-defined. Gene duplication and subsequent diversification give rise to three homologous kinesin I proteins (KIF5A, KIF5B and KIF5C) in vertebrates, but it is not clear whether and how they exhibit functional specificity. Here we show that knockdown of KIF5A or KIF5B differentially affects excitatory synapses and dendritic transport in hippocampal neurons. The functional specificities of the two kinesins are determined by their diverse carboxyl-termini, where arginine methylation occurs in KIF5B and regulates its function. KIF5B conditional knockout mice exhibit deficits in dendritic spine morphogenesis, synaptic plasticity and memory formation. Our findings provide insights into how expansion of the kinesin I family during evolution leads to diversification and specialization of motor proteins in regulating postsynaptic function.

Distinct role of 5′UTR sequences in dendritic trafficking of BDNF mRNA: additional mechanisms for the BDNF splice variants spatial code

“…Non-radioactive in situ hybridization for GFP coding sequence was analyzed by viewing stained cultures under bright-field illumination as previously described [ 3 ] using a Nikon AXM1200 digital camera on a Nikon E800 Microscope with interference contrast-equipped lens (60× magnification) and then analyzed with the image analysis program ImageJ (NIH). Apical dendrites of bona fide pyramidal neurons identified by morphological criteria have been linearized using the “Straighten” plugin [ 32 ] as previously described [ 33 ]. Dendrites were traced conservatively, starting from the base of dendrite after soma and up to the point in which in situ labeling was distinguishable.…”

Distinct role of 5’UTR sequences in dendritic trafficking of BDNF mRNA: additional mechanisms for the BDNF splice variants spatial code.

“…Densitometric analysis on non-radioactive in situ hybridization Non-radioactive in situ hybridization for GFP coding sequence was analyzed by viewing stained cultures under bright-eld illumination as previously described (3) using a Nikon AXM1200 digital camera on a Nikon E800 Microscope with interference contrast-equipped lens (60x magni cation) and then analyzed with the image analysis program ImageJ (NIH). Apical dendrites of bona de pyramidal neurons identi ed by morphological criteria have been linearized using the "Straighten" plugin (32) as previously described (33). Dendrites were traced conservatively, starting from the base of dendrite after soma and up to the point in which in situ labeling was distinguishable.…”

Dysregulation of protein synthesis and dendritic spine morphogenesis in ASD: studies in human pluripotent stem cells

“…Dendritic mRNA transport is first validated by the detection of mRNAs encoding microtubule-associated protein 2 (MAP2) in the dendrites of cultured hippocampal neurons [27]. The transport of mRNA transcripts depends on specific RNA-binding proteins (RBPs), which form ribonucleoprotein complexes with the dendritic mRNAs and transported to the distal dendrites via the action of motor proteins such as kinesin and dynein [28][29][30][31][32]. RBPs provide tight regulation in dendritic mRNA transport by repressing the translation during trafficking and release the transcripts at the endpoint for translation in response to neuronal activity [33].…”