title: Aldolase sequesters WASP and affects WASP/Arp2/3-stimulated actin dynamics.
abstract: In addition to its roles in sugar metabolism, fructose-1,6-bisphosphate aldolase (aldolase) has been implicated in cellular functions independent from these roles, termed "moonlighting functions." These moonlighting functions likely involve the known aldolase-actin interaction, as many proteins with which aldolase interacts are involved in actin-dependent processes. Specifically, aldolase interacts both in vitro and in cells with Wiskott-Aldrich Syndrome Protein (WASP), a protein involved in controlling actin dynamics, yet the function of this interaction remains unknown. Here, the effect of aldolase on WASP-dependent processes in vitro and in cells is investigated. Aldolase inhibits WASP/Arp2/3-dependent actin polymerization in vitro. In cells, knockdown of aldolase results in a decreased rate of cell motility and cell spreading, two WASP-dependent processes. Expression of exogenous aldolase rescues these defects. Whether these effects of aldolase on WASP-dependent processes were due to aldolase catalysis or moonlighting functions is tested using aldolase variants defective in either catalytic or actin-binding activity. While the actin-binding deficient aldolase variant is unable to inhibit actin polymerization in vitro and is unable to rescue cell motility defects in cells, the catalytically inactive aldolase is able to perform these functions, providing evidence that aldolase moonlighting plays a role in WASP-mediated processes.
authors.affiliation: Program in Molecular Biology, Cell Biology and Biochemistry, Boston University, Boston, Massachusetts 02215, USA.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Ritterson Lew
authors.forename: Dean R
authors.initials: DR
authors.lastname: Tolan
mesh_terms: D051378:Actin-Related Protein 3 / Q000235:genetics / Q000378:metabolism*; D000199:Actins / Q000235:genetics / Q000378:metabolism*; D000091302:Angiopoietin-Like Protein 2; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D005634:Fructose-Bisphosphate Aldolase / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D055785:Gene Knockdown Techniques; D051379:Mice; D041681:NIH 3T3 Cells; D011817:Rabbits; D051316:Wiskott-Aldrich Syndrome Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D051378:Actin-Related Protein 3; D000199:Actins; D000091302:Angiopoietin-Like Protein 2; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins; C485793:Angptl2 protein, mouse; D051316:Wiskott-Aldrich Syndrome Protein; D005634:Fructose-Bisphosphate Aldolase