Antagonistic roles of neurofilament subunits NF-H and NF-M against NF-L in shaping dendritic arborization in spinal motor neurons.
Dendrites play important roles in neuronal function. However, the cellular mechanism for the growth and maintenance of dendritic arborization is unclear. Neurofilaments (NFs), a major component of the neuronal cytoskeleton, are composed of three polypeptide subunits, NF-H, NF-M, and NF-L, and are abundant in large dendritic trees. By overexpressing each of the three NF subunits in transgenic mice, we altered subunit composition and found that increasing NF-H and/or NF-M inhibited dendritic arborization, whereas increasing NF-L alleviated this inhibition. Examination of cytoskeletal organization revealed that increasing NF-H and/or NF-M caused NF aggregation and dissociation of the NF network from the microtubule (MT) network. Increasing NF-H or NF-H together with NF-M further reduced NFs from dendrites. However, these changes were reversed by elevating the level of NF-L with either NF-H or NF-M. Thus, NF-L antagonizes NF-H and NF-M in organizing the NF network and maintaining a lower ratio of NF-H and NF-M to NF-L is critical for the growth of complex dendritic trees in motor neurons.
Kong
J
J
Worcester Foundation for Biomedical Research, Department of Pharmacology and Molecular Toxicology, University of Massachusetts Medical Center, Shrewsbury, Massachusetts 01545, USA.
Tung
V W
VW
Aghajanian
J
J
Xu
Z
Z
D000818:Animals; D048429:Cell Size; D003599:Cytoskeleton / Q000502:physiology; D003712:Dendrites / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000502:physiology*; D016900:Neurofilament Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D013116:Spinal Cord
D016900:Neurofilament Proteins; C044882:neurofilament protein L; C051774:neurofilament protein H; C061195:neurofilament protein M