title: KIF1Bβ transports dendritically localized mRNPs in neurons and is recruited to synapses in an activity-dependent manner.
abstract: KIF1Bβ is a kinesin-like, microtubule-based molecular motor protein involved in anterograde axonal vesicular transport in vertebrate and invertebrate neurons. Certain KIF1Bβ isoforms have been implicated in different forms of human neurodegenerative disease, with characterization of their functional integration and regulation in the context of synaptic signaling still ongoing. Here, we characterize human KIF1Bβ (isoform NM015074), whose expression we show to be developmentally regulated and elevated in cortical areas of the CNS (including the motor cortex), in the hippocampus, and in spinal motor neurons. KIF1Bβ localizes to the cell body, axon, and dendrites, overlapping with synaptic-vesicle and postsynaptic-density structures. Correspondingly, in purified cortical synaptoneurosomes, KIF1Bβ is enriched in both pre- and postsynaptic structures, forming detergent-resistant complexes. Interestingly, KIF1Bβ forms RNA-protein complexes, containing the dendritically localized Arc and Calmodulin mRNAs, proteins previously shown to be part of RNA transport granules such as Purα, FMRP and FXR2P, and motor protein KIF3A, as well as Calmodulin. The interaction between KIF1Bβ and Calmodulin is Ca(+2)-dependent and takes place through a domain mapped at the carboxy-terminal tail of the motor. Live imaging of cortical neurons reveals active movement by KIF1Bβ at dendritic processes, suggesting that it mediates the transport of dendritically localized mRNAs. Finally, we show that synaptic recruitment of KIF1Bβ is activity-dependent and increased by stimulation of metabotropic or ionotropic glutamate receptors. The activity-dependent synaptic recruitment of KIF1Bβ, its interaction with Ca(2+) sensor Calmodulin, and its new role as a dendritic motor of ribonucleoprotein complexes provide a novel basis for understanding the concerted co-ordination of motor protein mobilization and synaptic signaling pathways.
authors.affiliation: Department of Biological Sciences, University of Cyprus, University Avenue 1, 1678, Nicosia, Cyprus. despinacharalambous@yahoo.co.uk
authors.forename: Despina C
authors.initials: DC
authors.lastname: Charalambous
authors.forename: Emanuela
authors.initials: E
authors.lastname: Pasciuto
authors.forename: Valentina
authors.initials: V
authors.lastname: Mercaldo
authors.forename: Pietro
authors.initials: P
authors.lastname: Pilo Boyl
authors.forename: Sebastian
authors.initials: S
authors.lastname: Munck
authors.forename: Claudia
authors.initials: C
authors.lastname: Bagni
authors.forename: Niovi
authors.initials: N
authors.lastname: Santama
mesh_terms: D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism; D002147:Calmodulin / Q000378:metabolism; D045744:Cell Line, Tumor; D002490:Central Nervous System / Q000378:metabolism*; D003712:Dendrites / Q000378:metabolism*; D006801:Humans; D016547:Kinesins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D020409:Molecular Motor Proteins / Q000378:metabolism*; D009046:Motor Neurons / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000209:etiology; D020033:Protein Isoforms / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering; D017470:Receptors, Glutamate / Q000378:metabolism; D012261:Ribonucleoproteins / Q000378:metabolism*; D015398:Signal Transduction; D013572:Synaptic Vesicles / Q000378:metabolism*
chemical_list: D002147:Calmodulin; C091053:KIF1B protein, human; C490398:Kif1b protein, mouse; D020409:Molecular Motor Proteins; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D017470:Receptors, Glutamate; D012261:Ribonucleoproteins; D016547:Kinesins; D002118:Calcium