Assembly properties of dominant and recessive mutations in the small mouse neurofilament (NF-L) subunit

Steven R. Gill, Philip C. Wong, Mervyn J. Monteiro, Don W. Cleveland

Research output: Contribution to journalArticlepeer-review

Abstract

We have generated a set of amino- and carboxy-terminal deletions of the NF-L neurofilament gene and determined the assembly properties of the encoded subunits after coexpression with vimentin or wild-type NF-L. NF-L molecules missing >30% (31 amino acids of the head) or 90% (128 amino acids of the tail) failed to incorporate into intermediate filament networks. Carboxy-terminal deletions into the rod domain yield dominant mutants that disrupt arrays assembled from wild-type subunits, even when present at levels of -2% of the wild-type subunits. Even mutants retaining 55% of the tail (61 amino acids) disrupt normal arrays when accumulated above -10% of wild-type subunits. Since deletion of >90% of the head domain produces "recessive" assembly incompetent subunits that do not affect wild-type filament arrays, whereas smaller deletions yield efficient network disruption, we conclude that some sequence(s) in the head domain (within residues 31-87) are required for the earliest steps in filament assembly. Insertional mutagenesis in the nonhelical spacer region within the rod domain reveals that as many as eight additional amino acids can be tolerated without disrupting assembly competence.

Original languageEnglish (US)
Pages (from-to)2005-2019
Number of pages15
JournalJournal of Cell Biology
Volume111
Issue number5
DOIs
StatePublished - Nov 1990

ASJC Scopus subject areas

  • Cell Biology

Fingerprint Dive into the research topics of 'Assembly properties of dominant and recessive mutations in the small mouse neurofilament (NF-L) subunit'. Together they form a unique fingerprint.

Cite this