SCG10, a microtubule destabilizing factor, stimulates the neurite outgrowth by modulating microtubule dynamics in rat hippocampal primary cultured neurons

Abstract

Microtubule dynamics, one of the key elements in neurite outgrowth, is regulated by various regulatory factors to determine the behavior of the neuronal growth cone and to form the specialized neuronal shape. SCG10 is a neuron-specific stathmin protein with a potent microtubule destabilizing factor and is enriched in the growth cones of the developing neurons. We investigated the functional role of SCG10 in neurite outgrowth using rat hippocampal primary cultured neurons. Genetic manipulation of SCG10 using a short-interfering RNA duplex markedly decreased the SCG10 expression level and significantly suppressed neurite outgrowth. This result was confirmed by immunodepletion experiments. On the other hand, the protein transduction of SCG10 using a polyarginine tag stimulated neurite outgrowth. Such manipulation of the SCG10 expression level affected microtubule morphology within the growth cones. A decrease in the SCG10 level converted the morphology to a more stable state, while an increase converted the morphology to a more dynamic state. However, an excess of SCG10 induced neurite retraction due to an excess of microtubule disassembly. These results suggest that SCG10 serves as an important regulatory factor of growth cone motility by enhancing microtubule dynamics, possibly through increasing the catastrophe frequency.

Kidins220/ARMS Modulates the Activity of Microtubule-regulating Proteins and Controls Neuronal Polarity and Development

“…However, Kidins220/ARMS overexpression in young hippocampal neurons results in neurons bearing no neurites, Golgi apparatus fragmentation, and hampered neuronal viability. This phenotype resembles the one of hippocampal neurons overexpressing SCG10, characterized by a round shape (68). At present, we do not know if the cause of this phenotype is due to dramatic changes in microtubule dynamics, which could explain the lack of neuritic extensions, Golgi fragmentation, and toxicity in these young neurons.…”

“…In this way, they regulate diverse phases of neuronal morphogenesis, depending on the type of neurons studied and environmental cues (68,92). In cultured hippocampal neurons, Sclip knockdown increases axonal branching, whereas SCG10 down-regulation promotes growth cone expansion (66).…”

“…In other neuronal types, inhibition of SCG10 increases growth cone size and reduces axonal length (66,68). In contrast, Sclip specifically regulates axonal branching (66) and is also required for dendritic initiation and development in cerebellar Purkinje cells (37).…”

Axon Formation in Neocortical Neurons Depends on Stage-Specific Regulation of Microtubule Stability by the Dual Leucine Zipper Kinase–c-Jun N-Terminal Kinase Pathway

“…role in the growth cones of developing neurites/axons, where it binds to microtubules to keep them unstable (Grenningloh et al, 2004;Morii et al, 2006). The DLK-JNK pathway may be involved in stage 2/stage 3 transitions via a phosphorylation-dependent reduction in SCG10 activity (Antonsson et al, 1998;Grenningloh et al, 2004) in certain areas of the cell, such as the shaft of the presumptive axon.…”

Transcriptional profile of induced and primary neurons reveals new candidate genes for lineage reprogramming

“…Embryonic Lethal, Abnormal Vision, Drosophila-Like 4 (Elavl4), also known as Hu-Antigen D (HuD) is a RNA-binding protein involved in neuronal maturation [18], neurite outgrowth and dendritic maintenance [19]. Stathmin 3 (Stmn3) or SCG10-Like Protein (SCLIP) is also related to dendritic formation [20] and neurite outgrowth [21]. Zinc finger, CCHC domain containing 12 (Zcchc12) or SmadInteracting Zinc Finger Protein 1 (Szn1) is a protein used in BMP [22], AP-1 and CREB signalling [23] as a co-activator.…”