INVESTIGADORES
PIGINO Gustavo Fernando
artículos
Título:
Conventional kinesin holoenzymes are composed of heavy and light chain homodimers.
Autor/es:
DEBOER SR, YOU Y, SZODORAI A, KAMINSKA A, PIGINO G, NWABUISI E, WANG B, ESTRADA-HERNANDEZ T, KINS S, BRADY ST, MORFINI G. SOURCE
Revista:
BIOCHEMISTRY
Editorial:
AMER CHEMICAL SOC
Referencias:
Lugar: Washington; Año: 2008 vol. 47 p. 4535 - 4543
ISSN:
0006-2960
Resumen:
Conventional kinesin is a major microtubule-based motor protein
responsible for anterograde transport of various membrane-bounded
organelles (MBO) along axons. Structurally, this molecular motor protein
is a tetrameric complex composed of two heavy (kinesin-1) chains and
two light chain (KLC) subunits. The products of three kinesin-1
(kinesin-1A, -1B, and -1C, formerly KIF5A, -B, and -C) and two KLC
(KLC1, KLC2) genes are expressed in mammalian nervous tissue, but the
functional significance of this subunit heterogeneity remains unknown.
In this work, we examine all possible combinations among conventional
kinesin subunits in brain tissue. In sharp contrast with previous
reports, immunoprecipitation experiments here demonstrate that
conventional kinesin holoenzymes are formed of kinesin-1 homodimers.
Similar experiments confirmed previous findings of KLC homodimerization.
Additionally, no specificity was found in the interaction between
kinesin-1s and KLCs, suggesting the existence of six variant forms of
conventional kinesin, as defined by their gene product composition.
Subcellular fractionation studies indicate that such variants associate
with biochemically different MBOs and further suggest a role of
kinesin-1s in the targeting of conventional kinesin holoenzymes to
specific MBO cargoes. Taken together, our data address the combination
of subunits that characterize endogenous conventional kinesin. Findings
on the composition and subunit organization of conventional kinesin as
described here provide a molecular basis for the regulation of axonal
transport and delivery of selected MBOs to discrete subcellular
locations.