Calmodulin signaling via the IQ motif

Abstract

The IQ motif is widely distributed in both myosins and non-myosins and is quite common in the database that includes more than 900 Pfam entries. An examination of IQ motif-containing proteins that are known to bind calmodulin (CaM) indicates a wide diversity of biological functions that parallel the Ca 2+ -dependent targets. These proteins include a variety of neuronal growth proteins, myosins, voltage-operated channels, phosphatases, Ras exchange proteins, sperm surface proteins, a Ras Gap-like protein, spindle-associated proteins and several proteins in plants. The IQ motif occurs in some proteins with Ca 2+ -dependent CaM interaction where it may promote Ca 2+ -independent retention of CaM. The action of the IQ motif may result in complex signaling as observed for myosins and the L-type Ca 2+ channels and is highly localized as required for sites of neuronal polarized growth and plasticity, fertilization, mitosis and cytoskeletal organization. The IQ motif associated with the unconventional myosins also promotes Ca 2+ regulation of the vectorial movement of cellular constituents to these sites. Additional regulatory roles for this versatile motif seem likely. ß

A rescuable folding defective Nav1.1 (SCN1A) sodium channel mutant causes GEFS+: Common mechanism in Nav1.1 related epilepsies?

“…Conversely, Na v 1.1-R1916G was not rescued by β3 or Gβγ, which bind to the C-terminal domain. Also, calmodulin was able to rescue Na v 1.1-M1841T (Rusconi et al, 2007) but not Na v 1.1-R1916G; however, its lack of effect is expected because of the modification of an essential arginine of the IQ calmodulin binding motif caused by R1916G (Bahler and Rhoads, 2002). On the other end, the lack of effect of β3 is particularly notable, because β3 is structurally very similar to β1 and should share the same binding sites (Spampanato et al, 2004).…”

“…1C), is an important residue of the calmodulin binding IQ motif (Bahler and Rhoads, 2002), which is implicated in the modulation of several Na + channel isoforms (Young and Caldwell, 2005;Choi et al, 2006;Biswas et al, 2008), and we have shown that calmodulin can rescue hNa v 1.1-M1841T (Rusconi et al, 2007). Although R1916G should inhibit calmodulin binding, we tested the effect of cotransfection of calmodulin and found, indeed, that there was no significant modification of hNa v 1.1-R1916G current density ( Fig.…”

“…1B; c.5746A>G considering the ORF of GenBank sequence NM_006920.4) (Combi et al, 2007), corresponding to the missense mutation R1916G in the shorter splice variant (1998 amino acids) of the Na v 1.1 Na + channel α subunit, which replaces with a glycine an essential arginine within a well conserved IQ calmodulin binding motif (Bahler and Rhoads, 2002) located in the C-terminal cytoplasmic domain of Na v 1.1 (Fig 1C). The mutation should substantially inhibit the interaction with calmodulin and thus calmodulin-dependent modulation of the channel.…”

Myosin-Va Regulates Exocytosis through the Submicromolar Ca2+-dependent Binding of Syntaxin-1A

“…We demonstrated previously that exocytosis is regulated by Ca 2ϩ /CaM-dependent protein kinase II (CaMKII), which binds to syntaxin-1A in a Ca 2ϩ - dependent manner when it is autophosphorylated (Ohyama et al, 2002). Although the CaM-binding sites of myosin-Va and CaMKII are distinct (Bähler and Rhoads, 2002), their Ca 2ϩ -dependencies for syntaxin-1A binding are very similar. Our current studies also could explain the involvement of CaM in exocytosis (Sakaba and Neher, 2001) and other CaM-dependent interactions (Junge et al, 2004).…”

Calmodulin permanently associates with rat olfactory CNG channels under native conditions

“…4b). Between residues 183 and 193 of CNGB1b (LQELVKMEKER), CaM1 resembles a generalized IQ-type calmodulin-binding motif ({I,L,V}QxxxRxxxx{R,K}) 23 , which is understood to mediate binding of apocalmodulin [24][25][26] . A mutation affecting a single key residue, L183E, in this site specifically eliminated Ca 2+ -CaM modulation of heteromeric CNG channels, while at the same time maintaining the high cAMP sensitivity in the absence of Ca 2+ (Fig.…”