Muscle–Tendon Interactions in the Absence of Bones: Lessons from the Fruit Fly, Drosophila - Structural Interfaces and Attachments in Biology - page 122

interact genetically with the tendon-specific PS integrin receptors [ 23 ]. Such

an interaction might provide the muscle cell with a signal to arrest its migration.
The phenotype of kon - tiki / perdido is first detected during migration of the muscles;
however, an additional role in migration arrest cannot be excluded. LRT, a tendon-
specific leucine-rich transmembrane protein, accumulates following muscle arrival
and functionally interacts with Robo receptors on the muscle cell. Lack of lrt leads
to extra membrane extensions, suggesting aberrant muscle targeting and/or defects
in the arrest of muscle migration. Moreover, its overexpression stalls muscle
extension towards tendon cells, supporting the central role of this molecule in
promoting the targeting of muscle to tendon cells [ 16 ].
One possible mechanism for the arrest of muscle migration is the initiation of
MTJ formation. During muscle migration, the muscle is insensitive to ectopic
expression of the ECM protein, Tsp [ 17 ]. A possible explanation might be that
integrin receptors are not expressed on the membrane of migrating muscle cells.
The arrival of the muscle to its target tendon cell leads to the initial accumulation of
muscle integrin receptors, responsiveness to Tsp, and the accumulation of integrin
at the muscle ends. These initial adhesion events might represent a signal for the
muscle to arrest its migratory behavior and to initiate the formation of the MTJ. A
finding supporting this possibility is that overexpression of integrin in the muscle
during its migration leads to aberrant muscle migratory behavior [ 17 ].
In summary, several mechanisms explaining tendon recognition by the muscle
and its coupling to the initial formation of the MTJ are based on the function of
highly conserved proteins, which may play similar roles during the formation of the
MTJ in the vertebrate embryo. Recently, components of the intergin-mediated
adhesion machinery, including Talin 1 and Talin 2, as well as the laminin integrin
receptors

PS1

a b

1D were shown to actively mediate vertebrate MTJ, and
their absence was shown to lead to myopathies in humans [ 34 , 35 ].

a 7 b 1D and a 7B b

6.6 The Unique Tendon Cytoskeleton Enables Resistance
to Muscle Contractions

Fly tendons utilize the cuticle secreted by the ectoderm as an external skeleton.
Specialized proteins connect the tendon plasma membrane to the cuticle, maintaining
a tight association between the tendon cell and the exoskeleton [ 36 ]. However, the
tendon cell itself must resist muscle contraction in a flexible and elastic fashion. In
most cases, a single muscle is bound to a single tendon so that the mechanical strength
of muscle contraction is transmitted to a single cell and not to multiple tendons, as is
the case in vertebrate tendons [ 4 ]. Molecular insight into the mechanism enabling the
transmission of the contractile forces to the cuticle exoskeleton was deduced from an
RNAi-induced knock-down of the shortstop ( shot ) gene product in tendon cells.
Shortstop is a large evolutionarily conserved protein containing a microtubule bind-
ing sequence at its C' terminal domain, a large spectrin repeat domain, and plakin and