Multiple interactions of aluminum with neurofilament subunits: Regulation by phosphate-dependent interactions between C-terminal extensions of the high and middle molecular weight subunits
✍ Scribed by T. B. Shea; M. L. Beermann
- Book ID
- 102909684
- Publisher
- John Wiley and Sons
- Year
- 1994
- Tongue
- English
- Weight
- 636 KB
- Volume
- 38
- Category
- Article
- ISSN
- 0360-4012
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✦ Synopsis
Abstract
Exposure of individual purified neurofilament (NF) proteins to AlCl~3~ alters their electrophoretic properties in a time‐ and concentration‐dependent manner, as visualized by their failure to migrate into SDS gels. Co‐incubation of purified high (NF‐H) and middle (NF‐M) but not low (NF‐L) molecular weight NF subunits prevents this AlCl~3~‐induced alteration in electrophoretic migration. This latter finding suggested that specific interactions between NF‐H and NF‐M other than filament formation influenced their interaction with AlCl~3~. Co‐incubation of the 160 kDa α‐chymotryptic cleavage product of NF‐H (corresponding to the highly phosphorylated C‐terminal sidearm domain) with native NF‐M prevented alteration in subunit electrophoretic migration by AlCl~3~. By contrast, intact, dephosphorylated NF‐H subunits were unable to prevent AlCl~3~‐induced alteration of native NF‐M electrophoretic migration. Taken together, these findings suggest that phosphate‐dependent interactions between the sidearm extensions of NF‐H and NF‐M diminish the ability of AlCl~3~ to associate with either subunit in a manner that alters their electrophoretic migration. This interaction of NF‐H and NF‐M sidearms is SDS‐sensitive, while AlCl~3~‐induced alteration in electrophoretic migration of individual subunits is SDS‐resistant. Addition of SDS to mixtures of NF‐H and NF‐M subunits disrupted the protective effect, and promoted AlCl~3~‐induced alterations in subunit electrophoretic migration. These findings support and extend the current hypothesis that the ability of aluminum to interact with NF subunits is a function of subunit phosphorylation, assembly, and extent of neurofilament‐neurofilament cross‐linking. © 1994 Wiley‐Liss, Inc.