Table 1.

Actin Binding Proteins in the Lens

Protein	Known functions	Epithelial Cell Localization (age, species)	Fiber Cell Localization (age, species)	Interactions With Lens Proteins	Lens Phenotype of Knockouts, Mutants or Inhibitor Treatment	References
α-actinin	Cross-links actin filaments in an anti-parallel orientation	-	Vertices of cortical fiber cells (neonatal and adult rat)	-	-	(Lo et al., 1997; Sjoblom et al., 2008)
Adducin	Caps actin filament barbed ends in actin- spectrin network	-	Broad and short sides of fiber cells (adult, rat)	-	-	(Fowler, 2013; Kaiser et al., 1989)
Arp2/3 complex	Actin nucleation. Initiates branched actin filament assembly from preexisting filaments	Cytoplasm (adult, mouse)	Enriched at vertices of fiber cells (adult, mouse)	N-cadherin and cortactin in fiber cells (not epithelial cells)	-	(Amann and Pollard, 2001; Blanchoin et al., 2000; Leonard et al., 2011; Mullins et al., 1998)
Band 4.1	Binds to and stabilizes actin- spectrin network	Not present (embryo, chick)	Short sides of fiber cells (embryo, chick)	-	-	(Aster et al., 1986; Aster et al., 1984; Bagchi et al., 2004; Beebe et al., 2001; Fowler, 2013)
Band 4.9 (dematin)	Bundles actin filaments	-	Fiber cell membranes (adult, chick)	-	-	(Faquin et al., 1988; Fowler, 2013)
Cofilin	Binds to actin filaments causing depolymerization (cofilin is inactivated by phosphorylation)	-	-	-	Decreased phospho-cofilin and abnormal actin filament networks in RIP76/RALPB1 transgenic lenses; increased phospho-cofilin and abnormal secondary fiber cell migration and orientation in Rac1 conditional lens knockouts	(Bamburg et al., 1980; Maddala et al., 2011a; Nishida et al., 1984; Sahu et al., 2014)
Cortactin	Bind and stabilizes branched actin filaments and activated (phosphorylated) cortactin recruits Arp2/3 to polymerize actin filaments	Total and phospho- cortactin is enriched at vertices of hexagonal equatorial epithelial cells (adult, mouse)	-	-	Loss of EphA2 leads to changes in actin and cortactin localization in hexagonal equatorial epithelial cells of meridional rows	(Cheng et al., 2013; Uruno et al., 2001; Weaver et al., 2001)
Crystallin, α	Small heat shock proteins with chaperone-like functions	Cytoplasm (adult, mouse)	Cytoplasm (adult, mouse)	-	Mutations in α- crystallins alter association with actin, a possible native substrate of α-crystallins	(Andley et al., 2014; Bloemendal et al., 1984; Brown et al., 2007; Del Vecchio et al., 1984; Gopalakrishnan and Takemoto, 1992; Kibbelaar et al., 1979)
Crystallin, β/γ	Structural proteins	-	Cytoplasm (adult, mouse)	-	Interacts with actin, and γ- crystallins may help stabilize actin filaments in mature fiber cells	(Fan et al., 2012; Li et al., 2008; Rao et al., 2008)
Ezrin	In ERM/EPPD complexes that link actin filament networks with the plasma membrane	-	Broad and short sides of fiber cells (adult, bovine/mouse); enriched on sides of fiber cells (embryo, chick)	Aqp0, moesin, spectrin, plectin, periaxin, periplaxin, desmoyokin	Genetic variation linked to human age-related cataracts	(Bagchi et al., 2004; Bretscher, 1983; Lin et al., 2013; Maddala et al., 2011b; Straub et al., 2003; Wang and Schey, 2011)
Formin [isoform(s) unknown]	Nucleates unbranched actin networks by promoting barbed end filament assembly	Cytoplasm and nucleus (embryo, mouse)	Cytoplasm and nucleus (embryo, mouse)	-	Fiber cell degeneration	(de la Pompa et al., 1995; Goode and Eck, 2007; Pruyne et al., 2002; Sagot et al., 2002)
Gelsolin	Severs actin filaments and caps actin filament barbed ends	-	-	α-crystallins	-	(Andley et al., 2014; Yin and Stossel, 1980)
Myosin II	Bipolar filaments bind to anti- parallel actin filaments to generate filament sliding and contractility	Apical surface of lens vesicle (embryo, mouse); cytoplasm and concentrated at apical junction between epithelial and fiber cells (embryo and neonatal, mouse)	Cytoplasm (embryo and neonatal, mouse); basal membrane complexes (embryo, chick)	-	Mutations in humans and mice cause cataracts; inhibitor treatment leads abnormal eye cup and lens vesicle formation and nuclear cataracts (mouse) as well as decreased lens stiffness and changes in focal length (chick)	(Bassnett et al., 1999; Borges et al., 2011; Chauhan et al., 2009; De Rocco et al., 2013; Economou et al., 2012; Eiraku et al., 2011; Hao et al., 2012; Lang et al., 2014; Luck and Choh, 2011; Maddala et al., 2007; Plageman et al., 2011; Saposnik et al., 2014; Won et al., 2015; Zhang et al., 2012)
Plectin	Links actin and intermediate filaments to ERM/EPPD complexes	-	Broad and short sides of fiber cell membranes (adult, bovine)	Ezrin, moesin, periaxin, periplakin, desmoyokin, spectrin	-	(Andra et al., 1998; Fontao et al., 2001; Jiu et al., 2015; Sandilands et al., 1995; Straub et al., 2003; Weitzer and Wiche, 1987)
α2β2-spectrin	Spectrin tetramers cross- link actin filaments to form an isotropic network at the membrane, the membrane skeleton	-	Broad and short sides of fiber cells (adult, mouse)	Ezrin, moesin, periaxin, periplaxin, desmoyokin, ankyrin-B	-	(Cheng et al., 2015; Fowler, 2013; Gokhin et al., 2012; Nowak et al., 2009; Nowak and Fowler, 2012; Straub et al., 2003)
Tmod1 (mouse) Tmod4 (chicken)	Caps actin filament pointed ends, inhibiting actin association and dissociation, promoting length regulation and stability	Cytoplasm in differentiating equatorial epithelial cells (adult, mouse)	Broad and short sides of fiber cells; not at vertices (adult, mouse)	γTM (mouse), filensin (chick), spectrin, CP49 (indirect, mouse)	Abnormal actin- spectrin network, disrupted fiber cell packing, decreased lens stiffness and gap junction coupling	(Almenar-Queralt et al., 1999; Cheng et al., 2015; Fischer et al., 2003; Fischer et al., 2000; Fowler, 1996, 2013; Gokhin et al., 2012; Lee et al., 2000; Nowak et al., 2009; Nowak and Fowler, 2012; Sussman et al., 1996; Weber et al., 1994; Woo et al., 2000; Yamashiro et al., 2012)
Tropomyosin (γTM)	Binds along sides of actin filaments to prevent severing and depolymerization	Cytoplasm (adult, mouse)	Broad and short sides of fiber cells (adult, mouse)	Tmod1, Tmod4	-	(Fischer et al., 2000; Fowler, 2013; Lee et al., 2000; Nowak et al., 2009; Woo and Fowler, 1994)