Frem3, a member of the 12 CSPG repeats-containing extracellular matrix protein family, is a basement membrane protein with tissue distribution patterns distinct from those of Fras1, Frem2, and QBRICK/Frem1.
A novel protein family characterized by the presence of 12 CSPG repeats and Calx-beta domains includes Fras1, QBRICK/Frem1, Frem2 and Frem3. Although Fras1, QBRICK/Frem1 and Frem2 have been shown to localize at the basement membrane through reciprocal stabilization, it remains unclear whether Frem3 is also deposited at the basement membrane in a similar manner. Here we show that Frem3 localizes at the basement membrane with tissue distribution patterns clearly distinct from those of other 12 CSPG repeats-containing proteins (12-CSPG proteins). In adult mice, Frem3 was present at the basement membrane underlying ductal cells of the salivary gland, retinal ganglion cells, basal cells of epidermis and hair follicles, where other 12-CSPG proteins were barely expressed. In embryos and neonates, the expression of Frem3 transcripts was significantly lower than that of the other 12-CSPG proteins, although Frem3 protein was coexpressed with other 12-CSPG proteins at the basement membranes of retina, renal epithelia and epidermis. Interestingly, Frem3 deposition at the epidermal basement membrane was not severely compromised in blebbing mutant embryos, in which the basement membrane deposition of other 12-CSPG proteins was dramatically reduced due to the breakdown of their reciprocal stabilization. These results indicate that Frem3 is a basement membrane protein that is distinct from other 12-CSPG proteins in its tissue distribution and competence to assemble into the basement membrane.
Kiyozumi
Daiji
D
Laboratory of Extracellular Matrix Biochemistry, Institute for Protein Research, Osaka University, Suita, Osaka, 565-0871, Japan.
Sugimoto
Nagisa
N
Nakano
Itsuko
I
Sekiguchi
Kiyotoshi
K
D000818:Animals; D000831:Animals, Newborn; D001485:Basement Membrane / Q000378:metabolism*; D004628:Embryonic Structures / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D018859:Hair Follicle / Q000196:embryology / Q000378:metabolism; D007150:Immunohistochemistry; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D012160:Retina / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012469:Salivary Glands / Q000378:metabolism; D013997:Time Factors
D016326:Extracellular Matrix Proteins; C482018:Fras1 protein, mouse; C492585:Frem1 protein, mouse; C504802:Frem2 protein, mouse; C519661:Frem3 protein, mouse