Strumpellin (encoded by [WASHC5/KIAA0196](/genes/kiaa0196)) is a core structural component of the WASH complex that drives actin-dependent endosomal protein recycling. Mutations in strumpellin cause hereditary spastic paraplegia type 8 (SPG8) through impaired endosomal trafficking in long corticospinal tract axons.
Overview
Strumpellin is a 1,159-amino acid protein (~134 kDa) that serves as a scaffolding subunit of the pentameric WASH complex<sup>[1]</sup>. The WASH complex generates branched actin networks on endosomal membranes through activation of the Arp2/3 complex, providing the mechanical force required for membrane tubulation and cargo sorting<sup>[2]</sup>. Strumpellin is essential for WASH complex stability and function, and its disruption causes defects in endosomal recycling pathways that are critical for neuronal health. [@derivery2009]
Strumpellin is predicted to be a largely α-helical protein with coiled-coil regions<sup>[3]</sup>:
...
Strumpellin (KIAA0196/WASHC5 Protein)
Introduction
Strumpellin (encoded by [WASHC5/KIAA0196](/genes/kiaa0196)) is a core structural component of the WASH complex that drives actin-dependent endosomal protein recycling. Mutations in strumpellin cause hereditary spastic paraplegia type 8 (SPG8) through impaired endosomal trafficking in long corticospinal tract axons.
Overview
Strumpellin is a 1,159-amino acid protein (~134 kDa) that serves as a scaffolding subunit of the pentameric WASH complex<sup>[1]</sup>. The WASH complex generates branched actin networks on endosomal membranes through activation of the Arp2/3 complex, providing the mechanical force required for membrane tubulation and cargo sorting<sup>[2]</sup>. Strumpellin is essential for WASH complex stability and function, and its disruption causes defects in endosomal recycling pathways that are critical for neuronal health. [@derivery2009]
[Valdmanis PN et al., Mutations in the KIAA0196 gene at the SPG8 locus cause hereditary spastic paraplegia (2007) (2007)](https://doi.org/10.1086/519509)
[Derivery E et al., The Arp2/3 activator WASH controls the fission of endosomes through a large multiprotein complex (2009) (2009)](https://doi.org/10.1016/j.devcel.2009.09.010)
[Freeman C et al., The hereditary spastic paraplegia protein strumpellin: characterisation in neurons and of the effect of disease mutations on WASH complex assembly and function (2015) (2015)](https://doi.org/10.1016/j.bbadis.2014.10.011)
[Hao YH et al., USP7 acts as a molecular rheostat to promote WASH-dependent endosomal protein recycling (2015) (2015)](https://doi.org/10.1016/j.molcel.2015.09.033)
[McGough IJ et al., Retromer binding to FAM21 and the WASH complex is perturbed by the Parkinson disease-linked VPS35(D620N) mutation (2014) (2014)](https://doi.org/10.1016/j.cub.2014.07.004)