Cardiomyocytes - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 221

only proteins (FHL), also named skeletal muscle LIM domain-containing proteins
(SLIM), includes FHL1, or SLIM1, 57 FHL2, or SLIM3, 58 and FHL3, or SLIM2. 59
Four-and-a-half LIM domain-containing protein is a LIM-only protein that is
characterized by 4 LIM domains (double zinc finger sequences) and a single zinc
finger domain (LIM half-motif) in the N-terminus. Members of the FHL family can
homo- or heterodimerize.
Members of the FHL family are regulators of cell differentiation and remodeling
of the cytoskeleton. The FHL proteins act in extracellular signal-regulated kinase
signaling. In addition, at least some FHL proteins are transcriptional coactivators,
but with distinct affinity for CREB and CREM transcription factors [ 386 ]. These
members of the subclass-1A basic helix-loop-helix leucine zipper (bHLHzip)
transcription factors regulate proliferation and differentiation of various cell types.
They homodimerize and heterodimerize (CREB-CREM heterodimers) and then can
connect to the cAMP-responsive element (CRE) in the regulatory region of diverse
target genes. 60
Protein FHL2 can associate with α 3A -, α 3B -, α 7A -, and several β -integrin

subunits.

5.3.5.8 LIM-Only Protein Zyxin

Zyxin, a ubiquitous member of the LIM-only protein family, is involved in
cytoskeletal organization. It is mainly located in focal adhesion complexes close
to the Z disc. It binds to -actinin and cardiac (muscle)-specific LIM protein

(MLP or CLP), 61 a member of the C-reactive protein family that belongs to the
cardiomyocyte cytoskeleton.

α

5.3.5.9 Muscle/Cardiac-Specific LIM Protein

The Z disc of cardiomyocytes contains a stress sensor made of muscle-specific
LIM protein, titin-cap, and titin. Cardiac LIM protein binds to -actinin, telethonin,

nebulin-related actinin-binding protein NRAP, PP3 phosphatase, and

α

-spectrin.
Cultured cardiomyocytes deficient for MLP do not express natriuretic peptides ANP
and BNP in response to stretch.

β

57 Diverse FHL1 isoforms with different numbers of LIM domains can be generated by alternative
splicing.
58 A.k.a. downregulated in rhabdomyosarcoma LIM protein (DRAL).
59 Protein FHL5 corresponds to activator of cAMP-responsive element modulator (CREM) in testis
(ACT). Modulator CREM is a transcription factor that operates in the differentiation of spermatids
into mature spermatozoa. This zinc ion-binding molecule serves as transcription coactivator.
60 Protein FHL1 has a higher affinity for CREM expressed at high levels in spermatid cells. Both
FHL2 and FHL3 that are expressed mainly in the heart and skeletal muscle, respectively, interact
specifically with CREB. Protein FHL2 also binds to the androgen receptor.
61 A.k.a. cysteine-rich protein-3 (CRP3) or cysteine- and glycine-rich protein-3 (CSRP3).