A Role for the Cytoskeleton-associated Protein Palladin in Neurite Outgrowth

Abstract

The outgrowth of neurites is a critical step in neuronal maturation, and it is well established that the actin cytoskeleton is involved in this process. Investigators from our laboratory recently described a novel protein named palladin, which has been shown to play an essential role in organizing the actin cytoskeleton in cultured fibroblasts. We investigated the expression of palladin in the developing rat brain by Western blot and found that the E18 brain contained a unique variant of palladin that is significantly smaller (approximately 85 kDa) than the common form found in other developing tissues (90-92 kDa). Because the expression of a tissue-specific isoform suggests the possibility of a cell type-specific function, we investigated the localization and function of palladin in cultured cortical neurons. Palladin was found preferentially targeted to the developing axon but not the dendrites and was strongly localized to the axonal growth cone. When palladin expression was attenuated by transfection with antisense constructs in both the B35 neuroblastoma cell line and in primary cortical neurons, a reduction in the expression of palladin resulted in a failure of neurite outgrowth. These results implicate palladin as a critical component of the developing nervous system, with an important role in axonal extension.

Characterization of CLP36/Elfin/PDLIM1 in the nervous system

“…Palladin is an actin cross-linking protein and interacts with Ena/VASP and profilin which regulate actin polymerization (Goicoechea et al 2008). Palladin is concentrated in the growth cones and knockdown of palladin expression by an antisense technique led to the suppression of neurite outgrowth in primary cortical neurons (Boukhelifa et al 2001). In SAOS-2 cells, over-expression of the PDZ domain of CLP36 disturbed localization of palladin to stress fibers, suggesting a role of CLP36 in determining the intracellular localization of palladin (Maeda et al 2009).…”

Caenorhabditis elegansKettin, a Large Immunoglobulin-like Repeat Protein, Binds to Filamentous Actin and Provides Mechanical Stability to the Contractile Apparatuses in Body Wall Muscle

“…However, kettin might be functionally homologous to palladin (Parast and Otey, 2000), myopalladin (Bang et al, 2001), and myotilin (Salmikangas et al, 1999), which have two to five Ig-repeats and localize to the Z-lines of vertebrate striated muscle. These proteins are critical for actin filament reorganization in nonmuscle cells (Boukhelifa et al, 2001(Boukhelifa et al, , 2003Salmikangas et al, 2003;Otey et al, 2005) and myofibril assembly in muscle cells (Bang et al, 2001;Salmikangas et al, 2003;Otey et al, 2005). In particular, myotilin directly binds to actin filaments, and its mutations in the human gene are associated with limb girdle muscular dystrophy 1A (Salmikangas et al, 1999) and myofibrillar myopathy (Selcen and Engel, 2004), which are termed myotilinopathies (Goebel, 2005;Olive et al, 2005).…”

α‐actinin revisited: A fresh look at an old player

“…The interaction is mediated by a unique sequence conserved in palladin and myotilin, and the C-terminal CaM domain of ␣-actinin. Palladin's function has been explored in a variety of cell types, and it has been implicated as having an important role in both the maintenance of cytoskeletal organization and in the establishment of cell morphology [Parast and Otey, 2000;Mykkänen et al, 2001;Boukhelifa et al, 2001Boukhelifa et al, , 2003]. Down-regulation of palladin in cultured fibroblasts results in a striking loss of stress fibers and focal adhesions [Parast and Otey, 2000].…”