Phenotypes induced by NM causing α-skeletal muscle actin mutants in fibroblasts, Sol 8 myoblasts and myotubes

BMC Research Notes

Table 1 Description and results of the biochemical characterization of 16 new nemaline myopathy causing α-skeletal muscle actin mutants.

Mutant	phenotype	Folding	CAP	ABP	copol	In actin structure (Kabsch)	reference
WT		+	+	+	++
D25N	severe NEM ┼	+	+	+	++	Subdomain I, Close to ATP cleft	[4]
V35L	severe NEM	+	+	+	++	Subdomain II, Buried	[19]
P38L	severe NEM	+	+	+	+	Subdomain II	[19]
H73L	severe NEM ┼	+	-	+, VDBP+/-	+	Subdomain II, In ATP cleft, stabilizing interaction with D179	[19]
I75L	severe NEM	+	+	+, VDBP+/-	++	Subdomain II, In ATP cleft	[19]
E83K	Typical NEM	+/-	+	+	+ more aggr	Helix	[19]
R116H	Severe NEM ┼	+ +/-	+	+	+ more aggr	Subdomain I, Helix, close to ATP cleft	[4]
V163M	IRM	+/-	+	+	+ more aggr	Subdomain III, Buried, near ATP-cleft	[27]
Q246R	mild, typical and severe	+	+	+	++	Subdomain IV, Close to F-actin contact	[19, 20]
G251D	severe NEM	+	+/-	+	++	Subdomain IV, At surface	[19]
R256H	severe NEM	+	-	+	+	Subdomain IV, Close to F-actin contact	[2]
M269R	mild NEM	+	+	+	+	Subdomain IV, F-actin contact, hydrophobic plug	[21]

The properties investigated here are folding, binding to cyclase associated protein (CAP), binding to the actin binding proteins (ABP) thymosinβ4, DNAseI and Vitamin D binding protein (VDBP) and copolymerisation with rabbit α-skeletal muscle actin (copol). Also the location in the actin structure according to Kabsch et al. [18] is indicated, in addition to the patients phenotype as presented in the reference with NEM = nemaline myopathy, sarcoplasmic nemaline bodies; IRM = intranuclear rod myopathy.

ISSN: 1756-0500