title: Activation of Aplysia ARF6 induces neurite outgrowth and is sequestered by the overexpression of the PH domain of Aplysia Sec7 proteins.
abstract: ADP-ribosylation factors (ARFs) are small guanosine triphosphatases of the Ras superfamily involved in membrane trafficking and regulation of the actin cytoskeleton. Aplysia Sec7 protein (ApSec7), a guanine nucleotide exchange factor for ARF1 and ARF6, induces neurite outgrowth and plays a key role in 5-hydroxyltryptamine-induced neurite growth and synaptic facilitation in Aplysia sensory-motor synapses. However, the specific role of ARF6 signaling on neurite outgrowth in Aplysia neurons has not been examined. In the present study, we cloned Aplysia ARF6 (ApARF6) and revealed that an overexpression of enhanced green fluorescent protein (EGFP)-fused constitutively active ApARF6 (ApARF6-Q67L-EGFP) could induce neurite outgrowth in Aplysia sensory neurons. Further, we observed that ApARF6-induced neurite outgrowth was inhibited by the co-expression of a Sec7 activity-deficient mutant of ApSec7 (ApSec7-E159K). The pleckstrin homology domain of ApSec7 may bind to active ApARF6 at the plasma membrane and prevent active ApARF6-induced functions, including intracellular vacuole formation in HEK293T cells. The results of the present study suggest that activation of ARF6 signaling could induce neurite outgrowth in Aplysia neurons and may be involved in downstream signaling of ApSec7-induced neurite outgrowth in Aplysia neurons.
authors.affiliation: Department of Ecological Science, College of Ecology and Environment, Kyungpook National University, 2559, Gyeongsang-daero, Sangju-si, Gyeongsangbuk-do 37224, Republic of Korea. Electronic address: jangdj@knu.ac.kr.
authors.forename: Deok-Jin
authors.initials: DJ
authors.lastname: Jang
authors.affiliation: Department of Ecological Science, College of Ecology and Environment, Kyungpook National University, 2559, Gyeongsang-daero, Sangju-si, Gyeongsangbuk-do 37224, Republic of Korea.
authors.forename: Yong-Woo
authors.initials: YW
authors.lastname: Jun
authors.affiliation: Department of Biological Sciences, College of Natural Sciences, Seoul National University, 1, Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea.
authors.forename: Jaehoon
authors.initials: J
authors.lastname: Shim
authors.affiliation: Department of Biological Sciences, College of Natural Sciences, Seoul National University, 1, Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea.
authors.forename: Su-Eon
authors.initials: SE
authors.lastname: Sim
authors.affiliation: Department of Biotechnology and Biological Science, College of Life Science and Nano Technology, Hannam University, 1646, Yuseong-daero, Yuseong-gu, Daejeon 34054, Republic of Korea.
authors.forename: Jin-A
authors.initials: JA
authors.lastname: Lee
authors.affiliation: Department of Biological Sciences, College of Natural Sciences, Seoul National University, 1, Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea.
authors.forename: Chae-Seok
authors.initials: CS
authors.lastname: Lim
authors.affiliation: Department of Biological Sciences, College of Natural Sciences, Seoul National University, 1, Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea. Electronic address: kaang@snu.ac.kr.
authors.forename: Bong-Kiun
authors.initials: BK
authors.lastname: Kaang
mesh_terms: D020727:ADP-Ribosylation Factors / Q000378:metabolism*; D000818:Animals; D001048:Aplysia; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D016501:Neurites / Q000378:metabolism*; D000071446:Neuronal Outgrowth / Q000502:physiology*; D000070539:Pleckstrin Homology Domains / Q000502:physiology*; D011984:Sensory Receptor Cells / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013569:Synapses / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D020662:Guanine Nucleotide Exchange Factors; C066755:Sec7 guanine nucleotide exchange factors; D020727:ADP-Ribosylation Factors
keywords: ARF6; Aplysia; Neurite outgrowth; PH domain; Sec7; Synaptic facilitation