Abstract
The Arp2/3 complex generates branched actin networks at different locations of the cell. The WASH and WAVE Nucleation Promoting Factors (NPFs) activate the Arp2/3 complex at the surface of endosomes or at the cell cortex, respectively. In this review, we will discuss how these two NPFs are controlled within distinct, yet related, multiprotein complexes. These complexes are not spontaneously assembled around WASH and WAVE, but require cellular assembly factors. The centrosome, which nucleates microtubules and branched actin, appears to be a privileged site for WASH complex assembly. The actin and microtubule cytoskeletons are both responsible for endosome shape and membrane remodeling. Motors, such as dynein, pull endosomes and extend membrane tubules along microtubule tracks, whereas branched actin pushes onto the endosomal membrane. It was recently uncovered that WASH assembles a super complex with dynactin, the major dynein activator, where the Capping Protein (CP) is exchanged from dynactin to the WASH complex. This CP swap initiates the first actin filament that primes the autocatalytic nucleation of branched actin at the surface of endosomes. Possible coordination between pushing and pulling forces in the remodeling of endosomal membranes is discussed.
Highlights
Active movement of cells or within cells is fueled by dynamics of cytoskeletal elements, such as actin filaments and microtubules together with associated molecular motors
A number of answers have been proposed: short and freely diffusing actin filaments might be generated by cofilin-induced severing of previous filaments (Ichetovkin et al, 2002; Chen and Pollard, 2013), primer filaments might be nucleated by independent nucleators, such as formins or Spire (Zuchero et al, 2009; Isogai et al, 2015), or by the Arp2/3 complex itself activated in this case by atypical activators, such as SPIN90, which do not require a pre-existing filament (Wagner et al, 2013)
The WASH complex is composed of SWIP, Strumpellin, FAM21, WASH, and CCDC53 subunits
Summary
Active movement of cells or within cells is fueled by dynamics of cytoskeletal elements, such as actin filaments and microtubules together with associated molecular motors. Monomeric globular actin is polymerized into linear or branched structures of filamentous actin. E.g., stress fibers, can exert contractile forces by means of associated myosins, but branched actin structures generate forces, pushing forces in this case, by their mere polymerization. The key role of branched actin is to remodel membranes during cell migration, endocytosis and intracellular trafficking. Branched actin polymerization is due to a conserved and ubiquitous heptameric complex, the Arp2/3 complex, which nucleates a new actin filament off a pre-existing one (Pollard, 2007).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
