When I took a look at Hemmi, H. et al. ‘s paper several years ago, I almost automatically assumed Toll-like receptor 9 (TLR9) to be monomeric and span the cell membrane like this figure. However, I later noticed its dimeric model (see also Lichtman, M.A. et al. eds. Williams Hematology 7th ed. McGraw-Hill Medical 2005, p233.) and subcellular localization study which indicates that it is located to the endoplasmic reticulum (ER) of dendritic cells or macrophages. Furthermore, a more recent study shows that it can be localized also on the cell surface of non-immune cells.

So I wish to raise the following three questions:

1. Can we determine the stoichiometry of full-length human TLR9 using AFM in solution?

2. Is the stoichiometry tissue-dependent or not?

3. What translocates TLR9 from ER or cell surface to endosome?

Addendum primum:

Latz, E. et al. has recently discussed the conformational changes of dimeric human TLR9 induced by CpG DNA binding.

Addendum secundum:

I have just noticed a paper demonstrating expression of human TLR9 in prostate cancer cells.

(for its expression in other tissues, see here.)

Addendum tertium:

Is dimeric model predominant?

Addendum quartum:

For a recent application of AFM in dendritic cell research, see here.

Addendum quintum:

Are all TLRs dimeric?

Addendum sextum:

Is monomeric model of TLR9 still viable?

Addendum septimum:

Again, are all TLRs dimeric?

Addendum octavum:

Again, what translocates TLR9 from ER to lysosome?

Addendum nonum:

I have been unaware of TLR expression on airway epithelial cells.

Addendum decimum:

I wish to raise the following two questions about this paper and its Supplementary Figure 8.

Does human UNC93B(1) bind to human TLR9?

Is UNC93B itself a motor protein?

Addendum undecimum:

Again, is UNC93B itself a motor protein?

Addendum duodecimum:

I have just noticed this paper.

Addendum tertium decimum:

Are all TLRs monomeric?

Addendum quartum decimum:

Will the author(s) of this paper employ yeast two-hybrid method?

Addendum quintum decimum:



Addendum sextum decimum: