EFA6A encodes two isoforms with distinct biological activities in neuronal cells

Abstract

The processes of neurite extension and remodeling require a close coordination between the cytoskeleton and the cell membranes. The small GTPase ARF6 (ADP-ribosylation factor 6) has a central role in regulating membrane traffic and actin dynamics, and its activity has been demonstrated to be involved in neurite elaboration. EFA6A has been shown to act as a guanine nucleotide exchange factor (GEF) for ARF6. Here, we report that two distinct isoforms of the EFA6A gene are expressed in murine neural tissue: a long isoform of 1025 amino acids (EFA6A), and a short isoform of 393 amino acids (EFA6As). EFA6A encompasses proline-rich regions, a Sec7 domain (mediating GEF activity on ARF6), a PH domain, and a C-terminal region with coiled-coil motifs. EFA6As lacks the Sec7 domain, and it comprises the PH domain and the C-terminal region. The transcript encoding EFA6As is the result of alternative promoter usage. EFA6A and EFA6As have distinct biological activities: upon overexpression in HeLa cells, EFA6A induces membrane ruffles, whereas EFA6As gives rise to cell elongation; in primary cortical neurons EFA6A promotes neurite extension, whereas EFA6As induces dendrite branching. Our findings suggest that EFA6A could participate in neuronal morphogenesis through the regulated expression of two functionally distinct isoforms.

EFA6A, a guanine nucleotide exchange factor for Arf6, interacts with sorting nexin‐1 and regulates neurite outgrowth

“…It was recently shown that EFA6A promotes neurite extension, whereas EFA6s induces dendritic branching in cultured cortical neurons (Sironi et al . ). In mature neurons, the EFA6A‐Arf6 pathway regulates the development and maintenance of dendritic spines through the internalization of telencephalin and the downstream activation of the Rac1 pathway (Choi et al .…”

“…EFA6A is a prototypical member of this family that coordinates endocytic trafficking with actin cytoskeleton reorganization (Franco et al 1999). The murine EFA6A gene gives rise to two splice variants, a 1025-aminoacid polypeptide (EFA6A) with a long N-terminal region containing a Sec-7 domain required for GEF activity toward Arf6 and a 393-amino-acid polypeptide (EFA6As) sharing a C-terminal 327-amino-acid region but lacking a Sec-7 domain, by the use of an alternative promoter (Sironi et al 2009). In the mouse brain, EFA6A, EFA6C, and EFA6D exhibit isoform-specific spatiotemporal expression.…”

Visual Search of Neuropil-Enriched RNAs from Brain In Situ Hybridization Data through the Image Analysis Pipeline Hippo-ATESC

“…In particular, manual inspection revealed that this list contains some of the best known examples of transcripts localized to dendrites and/or associated with dendritic functions. Indeed, besides to a Camk2a probe not included in the training set, the list contained probes from Dendrin (Dnd) [35], [36], Psd (also known as Efa6a) [37], microtubule-associated protein 2 (Map2) [9], Git1 [38] and Spinophilin (Ppp1r9b) [39], [40]. Accordingly, visual inspection of the corresponding ABA images confirmed a significant signal enrichment in neuropil for many of the probes included in the list Table 2, as it is the case for the Rnf10 gene (Fig.…”

Microarray Expression Analysis for the Paradoxical Roles ofAcanthopanax senticosusHarms in Treating α-Synucleinopathies

“…Pcdh20, Cldn22, and Rnd1 may participate in cell adhesion, and the genetic variations in this process can cause synaptic dysfunction in PD (Chapman, ). The dysregulations of Psd, Cntnap1, and Capn11 can induce cytoskeletal abnormalities (Garcia‐Fresco et al ., ; Jetten et al ., ; Sironi et al ., ), which is linked to the pathogenesis of PD (Mila et al ., ). Nmbr can regulate the functions of 5‐hydroxytryptamine system (Yamano et al ., ), which may be involved in the development of PD through its interaction with the basal ganglia (Miguelez et al ., ).…”