Kif1Bβ isoform is enriched in motor neurons but does not change in a mouse model of amyotrophic lateral sclerosis

Abstract

The kinesin superfamily motor protein Kif1B is expressed in two isoforms, Kif1Balpha and Kif1Bbeta, with distinct cargo-binding domains. We examined the mRNA distribution of the two isoforms in adjacent sections of brain and spinal cord of adult mice using in situ hybridization analysis. Kif1Bbeta mRNA is enriched in several regions of brain and spinal cord. Its levels are four to five times higher than that of the alpha isoform, which was barely detectable. The highest mRNA levels of Kif1Bbeta were found in the cortex, hippocampus, cerebellum and the grey matter of the spinal cord. At the cellular level the highest signal was found in motor neurons in the motor nuclei of medulla oblongata and the ventral horn of spinal cord. Because expression of other Kif genes is altered in amyotrophic lateral sclerosis (ALS) models, we examined the expression level of Kif1Bbeta mRNA in the spinal cord of transgenic mice carrying the SOD1G93A mutation, a model of familial ALS, at presymptomatic and early stages of the disease. No changes were observed in Kif1Bbeta mRNA in motor neurons or in other regions of the spinal cord. These findings indicate that Kif1Balpha, which modulates the transport of mitochondria, may play a major role in tissues other than the central nervous system. Instead Kif1Bbeta, responsible for the transport of synaptic vesicle precursors, seems to play an important role in the nervous system, particularly in the lower motor neurons. The absence of changes of Kif1Bbeta mRNA in transgenic SOD1G93A mice suggests that other molecular mechanisms may play a role in the disruption of axonal transport occurring in the motor neurons of these mice.

Deregulated expression of cytoskeleton related genes in the spinal cord and sciatic nerve of presymptomatic SOD1G93A Amyotrophic Lateral Sclerosis mouse model

“…From those genes, only Kif3a and Kif1b or related molecules have been studied in the context of kinesin dysfunction or impaired anterograde transport of cargos, like neurofilament, in ALS (Dupuis et al, 2000; Conforti et al, 2003; Pantelidou et al, 2007). The Kif3a (downregulation) and Kif1b (upregulation) deregulated genes seen in the spinal cord of 40 days old SOD1 G93A mice were in line with descriptions of reduction KIF3Aβ in motor cortices of ALS human and animal model (Pantelidou et al, 2007) and of KIF3-associated proteins in ALS rodents (Dupuis et al, 2000), thus underlining the presence of an early and complex mechanism involved in the impairment of the fast anterograde axonal transport machinery in ALS prior motor neuron degeneration.…”

“…Microarray analyses identified the differentially expressed Kif1b in the spinal cord (40 days old mice) and sciatic nerve (60 days old mice) and it was the only gene that its product has been described in the context of ALS (Conforti et al, 2003; Pantelidou et al, 2007). The gene was then selected for verification by qPCR in the whole spinal cord (40 days old mice) and sciatic nerve (60 days) as well as in the enriched motor neurons and Schwann cells.…”

Microarray Profile of Brain Aging-Related Genes in the Frontal Cortex of SAMP8

“…is known Table 1 Brain aging-related orthologous genes found in the frontal cortex of the SAMP8 which are comparable to the study by Lu et al (2004) Figure 1 RT-PCR analysis of the transcription level changes of the four proposed orthologous genes in the 4-and 12-month-old frontal cortex of SAMP8. GAPDH was used as an internal control to modulate the transportation of mitochondria, while Kif1Bβ is responsible for transporting synaptic vesicle precursors in the nervous system (Conforti et al 2003).…”

Kinesin Expression in the Central Nervous System of Humans and Transgenic hSOD1G93A<b> </b>Mice with Amyotrophic Lateral Sclerosis

“…Moreover, point mutations in the motor domain of KIF5A were linked to hereditary spastic paraplegia, a disease affecting the upper motor neuron [24]. Mutations within the KIF5A lead to the axonal transport impairment via relenting or alteration of cargo binding [25]. Since not only retrograde, but also anterograde axonal transport seem to be altered in ALS, in the present work we investigated the expression profile of kinesins involved in both types of transport (KIF5A, KIF5C, KIF1B - anterograde, KIFC2/C3 - retrograde).…”