TY - GEN
T1 - The function of oligomerization-incompetent RDS in rods
AU - Chakraborty, Dibyendu
AU - Conley, Shannon M.
AU - Fliesler, Steven J.
AU - Naash, Muna I.
PY - 2010
Y1 - 2010
N2 - The photoreceptor-specific tetraspanin glycoprotein RDS (retinal degeneration slow) is associated with many forms of inherited retinal disease. RDS shares features in common with other tetraspanin proteins, including the existence of a large intradiscal D2 loop containing several cysteines. While these cysteines are used only for intramolecular disulfide bonds in most tetraspanins, RDS expresses a seventh, unpaired cysteine (C150) used for intermolecular disulfide bonding in the formation of large RDS oligomers. To study oligomerization-dependent vs. oligomerization-independent RDS functions in rods, we generated a transgenic mouse line harboring a point mutation that replaces this Cys with Ser (C150S), leading to the expression of an RDS protein that cannot form intermolecular disulfide bonds. The mouse opsin promoter (MOP) was used to direct C150S RDS expression specifically in rods in these transgenic mice (MOP-T). Here we report improvement in scotopic ERGs in MOP-T/rds +/- mice (compared to non-transgenic rds+/- controls) and the appearance of malformed outer segments (OSs) in MOP-T mice that do not express native RDS (MOP-T/rds-/-). These results suggest that while normal OS structure and function require RDS oligomerization, some RDS function is retained in the absence of C150. Since one of the functions of other tetraspanin proteins is to promote assembly of a membrane microdomain known as the "tetraspanin web", future studies may investigate whether assembly of this web is one of RDS's oligomerization-independent functions.
AB - The photoreceptor-specific tetraspanin glycoprotein RDS (retinal degeneration slow) is associated with many forms of inherited retinal disease. RDS shares features in common with other tetraspanin proteins, including the existence of a large intradiscal D2 loop containing several cysteines. While these cysteines are used only for intramolecular disulfide bonds in most tetraspanins, RDS expresses a seventh, unpaired cysteine (C150) used for intermolecular disulfide bonding in the formation of large RDS oligomers. To study oligomerization-dependent vs. oligomerization-independent RDS functions in rods, we generated a transgenic mouse line harboring a point mutation that replaces this Cys with Ser (C150S), leading to the expression of an RDS protein that cannot form intermolecular disulfide bonds. The mouse opsin promoter (MOP) was used to direct C150S RDS expression specifically in rods in these transgenic mice (MOP-T). Here we report improvement in scotopic ERGs in MOP-T/rds +/- mice (compared to non-transgenic rds+/- controls) and the appearance of malformed outer segments (OSs) in MOP-T mice that do not express native RDS (MOP-T/rds-/-). These results suggest that while normal OS structure and function require RDS oligomerization, some RDS function is retained in the absence of C150. Since one of the functions of other tetraspanin proteins is to promote assembly of a membrane microdomain known as the "tetraspanin web", future studies may investigate whether assembly of this web is one of RDS's oligomerization-independent functions.
UR - https://www.scopus.com/pages/publications/78649482659
U2 - 10.1007/978-1-4419-1399-9_5
DO - 10.1007/978-1-4419-1399-9_5
M3 - Conference contribution
C2 - 20238000
AN - SCOPUS:78649482659
SN - 9781441913982
T3 - Advances in Experimental Medicine and Biology
SP - 39
EP - 46
BT - Retinal Degenerative Diseases
A2 - Anderson, Robert
A2 - Mandal, Nawajes
A2 - Hollyfield, Joe
A2 - LaVail, Matthew
ER -