Structural basis for isoform-specific kinesin-1 recognition of Y-acidic cargo adaptors.

The light chains (KLCs) of the heterotetrameric microtubule motor kinesin-1, that bind to cargo adaptor proteins and regulate its activity, have a capacity to recognize short peptides via their tetratricopeptide repeat domains (KLC). Here, using X-ray crystallography, we show how kinesin-1 recognizes a novel class of adaptor motifs that we call 'Y-acidic' (tyrosine flanked by acidic residues), in a KLC-isoform-specific manner. Binding specificities of Y-acidic motifs (present in JIP1 and in TorsinA) to KLC1 are distinct from those utilized for the recognition of W-acidic motifs, found in adaptors, that are KLC-isoform non-selective.

SKIP controls lysosome positioning using a composite kinesin-1 heavy and light chain-binding domain.

The molecular interplay between cargo recognition and regulation of the activity of the kinesin-1 microtubule motor is not well understood. Using the lysosome adaptor SKIP (also known as PLEKHM2) as model cargo, we show that the kinesin heavy chains (KHCs), in addition to the kinesin light chains (KLCs), can recognize tryptophan-acidic-binding determinants on the cargo when presented in the context of an extended KHC-interacting domain. Mutational separation of KHC and KLC binding shows that both interactions are important for SKIP-kinesin-1 interaction and that KHC binding is important for lysosome transport However, in the absence of KLCs, SKIP can only bind to KHC when autoinhibition is relieved, suggesting that the KLCs gate access to the KHCs.

Binding of Myomesin to Obscurin-Like-1 at the Muscle M-Band Provides a Strategy for Isoform-Specific Mechanical Protection.

The sarcomeric cytoskeleton is a network of modular proteins that integrate mechanical and signaling roles. Obscurin, or its homolog obscurin-like-1, bridges the giant ruler titin and the myosin crosslinker myomesin at the M-band. Yet, the molecular mechanisms underlying the physical obscurin(-like-1):myomesin connection, important for mechanical integrity of the M-band, remained elusive.

Motor versus body awareness: Voxel-based lesion analysis in anosognosia for hemiplegia and somatoparaphrenia following right hemisphere stroke.

Anosognosia for hemiplegia (AHP) is informative about the neurocognitive basis of motor awareness. However, it is frequently associated with concomitant symptoms, such as hemispatial neglect and disturbances in the sense of body ownership (DSO). Although double dissociations between these symptoms have been reported, there is ongoing debate about whether they are manifestations of independent abnormalities, or a single neurocognitive deficit.

The Dynamic Localization of Cytoplasmic Dynein in Neurons Is Driven by Kinesin-1.

Cytoplasmic dynein, the major motor driving retrograde axonal transport, must be actively localized to axon terminals. This localization is critical as dynein powers essential retrograde trafficking events required for neuronal survival, such as neurotrophic signaling. Here, we demonstrate that the outward transport of dynein from soma to axon terminal is driven by direct interactions with the anterograde motor kinesin-1.